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    Clinical Trial Results:
    An Open Label, Dose-Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetics of TAK-981 in Adult Patients With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies

    Summary
    EudraCT number
    2020-003947-27
    Trial protocol
    PL   ES   BE  
    Global end of trial date
    14 Dec 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    09 Nov 2024
    First version publication date
    09 Nov 2024
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    TAK-981-1002
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03648372
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Dec 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Dec 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of phase 1 was to determine the safety and tolerability of TAK-981 as a single agent in participants with advanced or metastatic solid tumors and lymphomas and to establish the recommended phase 2 dose (RP2D) of TAK-981 and for phase 2 was to evaluate preliminary efficacy of TAK-981 in participants with select solid tumors or relapsed/refractory CD20+ non-Hodgkin lymphoma (NHL) indications.
    Protection of trial subjects
    This study was conducted with the highest respect for the individual participants, according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the informed consent regulations stated in Title 21 CFR, Part 50, in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) GCP E6 §4.8, and all applicable local regulations. Each investigator conducted the study according to applicable local or regional regulatory requirements and aligned his or her conduct in accordance with the responsibilities of the investigator. The Declaration of Helsinki ethical principles were addressed through the protocol and appendices containing requirements for informed consent and investigator responsibilities.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Oct 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 92
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    China: 2
    Worldwide total number of subjects
    109
    EEA total number of subjects
    15
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    66
    From 65 to 84 years
    43
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants took part in the study at 17 investigative sites in Poland, Belgium, Spain, the United States and China from 01 October 2018 to 14 December 2023.

    Pre-assignment
    Screening details
    Participants were enrolled in Phase 1 (Dose Escalation) and in Phase 2 (Dose Expansion) to receive TAK-981 doses.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Phase 1, Dose Escalation: TAK-981 3 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 3 milligram (mg), infusion, intravenously, twice weekly (BIW) on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 3 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 6 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 6 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 6 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 10 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 10 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 10 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 15 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 15 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 15 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 25 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 25 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 25 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 40 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 40 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 40 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 60 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 60 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 60 mg QW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, once weekly (QW) on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 60 mg, infusion, intravenously, on Days 1 and 8 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 75 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 75 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 75 mg QW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 75 mg, infusion, intravenously, on Days 1 and 8 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 90 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 90 mg QW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1 and 8 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1, 8 and 15 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 8 and 15 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 120 mg BIW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 120 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 1, Dose Escalation: TAK-981 120 mg QW
    Arm description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 120 mg, infusion, intravenously, on Days 1 and 8 in a 21-day treatment cycle in Phase 1.

    Arm title
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW
    Arm description
    Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Arm title
    Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW
    Arm description
    Participants with cervical cancer received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Arm title
    Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW
    Arm description
    Participants with microsatellite-stable colorectal cancer (MSS-CRC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Arm title
    Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW
    Arm description
    Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) progressed or relapsed after chimeric antigen receptor (CAR) T-cell therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Arm title
    Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW
    Arm description
    Participants with relapsed/refractory DLBCL that have not received prior cellular therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Arm title
    Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Arm description
    Participants with relapsed/refractory follicular lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.
    Arm type
    Experimental

    Investigational medicinal product name
    TAK-981
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    TAK-981 was administered as 90 mg, infusion, intravenously, on Days 1, 4, 8 and 11 in a 21-day treatment cycle in Phase 2.

    Number of subjects in period 1
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Started
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    7
    3
    7
    4
    3
    1
    Completed
    1
    0
    0
    0
    1
    1
    2
    1
    1
    1
    2
    2
    1
    1
    0
    1
    1
    1
    4
    2
    1
    Not completed
    4
    3
    4
    3
    3
    3
    5
    5
    5
    5
    6
    5
    6
    7
    6
    6
    2
    6
    0
    1
    0
         Consent withdrawn by subject
    2
    -
    -
    -
    -
    1
    2
    -
    -
    -
    2
    -
    2
    -
    -
    -
    1
    -
    -
    -
    -
         Start of a New Systemic Treatment
    -
    -
    -
    -
    -
    -
    -
    2
    -
    -
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
         Progressive Disease
    2
    3
    4
    3
    2
    2
    3
    3
    5
    5
    2
    3
    3
    3
    6
    -
    -
    -
    -
    -
    -
         Unspecified
    -
    -
    -
    -
    1
    -
    -
    -
    -
    -
    1
    2
    1
    3
    -
    5
    1
    5
    -
    1
    -
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    1
    -
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1, Dose Escalation: TAK-981 3 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 3 milligram (mg), infusion, intravenously, twice weekly (BIW) on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 6 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 6 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 10 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 10 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 15 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 15 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 25 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 25 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 40 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 40 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 60 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 60 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, once weekly (QW) on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 75 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 75 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1, 8 and 15 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 120 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 120 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW
    Reporting group description
    Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW
    Reporting group description
    Participants with cervical cancer received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW
    Reporting group description
    Participants with microsatellite-stable colorectal cancer (MSS-CRC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) progressed or relapsed after chimeric antigen receptor (CAR) T-cell therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory DLBCL that have not received prior cellular therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory follicular lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW Total
    Number of subjects
    5 3 4 3 4 4 7 6 6 6 8 7 7 8 6 7 3 7 4 3 1
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    59.8 ( 9.78 ) 61.0 ( 14.73 ) 52.0 ( 11.05 ) 66.7 ( 10.69 ) 59.5 ( 5.80 ) 65.0 ( 4.69 ) 59.3 ( 10.21 ) 62.5 ( 9.07 ) 60.8 ( 10.87 ) 62.3 ( 10.97 ) 60.5 ( 9.56 ) 62.4 ( 14.21 ) 64.4 ( 7.93 ) 59.4 ( 11.02 ) 57.8 ( 8.33 ) 64.0 ( 6.98 ) 53.3 ( 2.08 ) 51.6 ( 13.02 ) 56.3 ( 18.06 ) 71.7 ( 5.51 ) 53.0 ( 99999 ) -
    Gender categorical
    Units: Subjects
        Female
    4 2 2 2 2 2 3 2 4 4 3 5 4 3 5 1 3 3 0 3 1 58
        Male
    1 1 2 1 2 2 4 4 2 2 5 2 3 5 1 6 0 4 4 0 0 51
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Asian
    0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 2 0 1 1 6
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Black or African American
    0 0 0 0 0 0 2 2 2 0 1 0 0 1 0 0 0 1 0 0 0 9
        White
    5 3 4 3 3 4 4 4 4 6 7 6 7 5 5 7 3 2 4 2 0 88
        More than one race
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1
        Unknown or Not Reported
    0 0 0 0 1 0 0 0 0 0 0 0 0 2 1 0 0 1 0 0 0 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 0 0 0 1 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 3
        Not Hispanic or Latino
    5 3 4 2 3 4 7 6 6 6 6 6 6 6 5 7 3 7 4 3 1 100
        Unknown or Not Reported
    0 0 0 1 0 0 0 0 0 0 1 1 1 1 1 0 0 0 0 0 0 6

    End points

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    End points reporting groups
    Reporting group title
    Phase 1, Dose Escalation: TAK-981 3 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 3 milligram (mg), infusion, intravenously, twice weekly (BIW) on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 6 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 6 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 10 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 10 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 15 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 15 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 25 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 25 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 40 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 40 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 60 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 60 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, once weekly (QW) on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 75 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 75 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1, 8 and 15 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 120 mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1, Dose Escalation: TAK-981 120 mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW
    Reporting group description
    Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW
    Reporting group description
    Participants with cervical cancer received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW
    Reporting group description
    Participants with microsatellite-stable colorectal cancer (MSS-CRC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) progressed or relapsed after chimeric antigen receptor (CAR) T-cell therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory DLBCL that have not received prior cellular therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory follicular lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Primary: Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) [1] [2]
    End point description
    TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. Any abnormal laboratory results were considered as TEAEs. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    Units: participants
    4
    3
    4
    3
    4
    4
    6
    6
    5
    6
    8
    7
    7
    8
    6
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With Grade 3 or Higher TEAEs

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    End point title
    Phase 1: Number of Participants With Grade 3 or Higher TEAEs [3] [4]
    End point description
    The severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was life-threatening consequences; urgent intervention indicated, and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    Units: participants
    2
    2
    3
    1
    2
    2
    4
    3
    4
    0
    6
    5
    4
    7
    3
    No statistical analyses for this end point

    Primary: Phase 1: Duration of TEAEs

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    End point title
    Phase 1: Duration of TEAEs [5] [6]
    End point description
    TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    Units: days
        median (full range (min-max))
    3.0 (1 to 37)
    4.0 (1 to 21)
    1.0 (1 to 33)
    3.0 (1 to 5)
    4.0 (1 to 39)
    9.5 (1 to 36)
    4.0 (1 to 42)
    3 (1 to 47)
    8.0 (1 to 82)
    2.0 (1 to 58)
    4.5 (1 to 188)
    5.0 (1 to 37)
    2.0 (1 to 80)
    3.0 (1 to 131)
    4.0 (1 to 64)
    No statistical analyses for this end point

    Primary: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

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    End point title
    Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) [7] [8]
    End point description
    DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (>=) 3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities that were considered by the investigator to be related to study drug and dose-limiting. DLT-evaluable analysis set consisted of participants in dose escalation who received all Cycle 1 doses of TAK-981 without experiencing a DLT or who had a DLT during Cycle 1 of the study.
    End point type
    Primary
    End point timeframe
    Cycle 1 (Cycle length is equal to [=] 21 days)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    3
    3
    4
    3
    4
    4
    6
    5
    5
    6
    6
    6
    7
    6
    6
    Units: participants
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    0
    No statistical analyses for this end point

    Primary: Phase 2: Overall Response Rate (ORR)

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    End point title
    Phase 2: Overall Response Rate (ORR) [9] [10]
    End point description
    ORR was defined as percentage of participants who achieved complete response (CR) or partial response (PR) during the study as determined by the investigator according to response assessments based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 11.2 months)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    7
    3
    6
    4
    3
    1
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 40.96)
    0.0 (0.0 to 70.76)
    0.0 (0.0 to 45.93)
    0.0 (0.0 to 60.24)
    0.0 (0.0 to 70.76)
    100.0 (2.50 to 100.0)
    No statistical analyses for this end point

    Secondary: Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981

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    End point title
    Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 [11]
    End point description
    Cmax for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    7
    8
    5
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,7,8,5
    14.0 ( 74.6 )
    22.5 ( 19.7 )
    46.1 ( 45.3 )
    61.0 ( 69.0 )
    124 ( 80.9 )
    314 ( 37.8 )
    417 ( 33.4 )
    446 ( 27.4 )
    738 ( 37.1 )
    685 ( 30.4 )
    773 ( 49.3 )
    887 ( 54.5 )
    668 ( 32.9 )
    1410 ( 46.8 )
    1100 ( 36.4 )
        C1D8:n=0,2,4,3,3,4,6,5,5,6,6,6,6,6,5
    99999 ( 99999 )
    22.5 ( 22.8 )
    33.8 ( 35.7 )
    114 ( 103.6 )
    108 ( 39.2 )
    428 ( 49.9 )
    343 ( 26.6 )
    405 ( 35.6 )
    846 ( 33.3 )
    923 ( 69.0 )
    654 ( 57.5 )
    852 ( 66.2 )
    653 ( 69.6 )
    1460 ( 65.7 )
    825 ( 22.3 )
    No statistical analyses for this end point

    Secondary: Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981

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    End point title
    Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 [12]
    End point description
    Tmax for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    7
    8
    5
    Units: hours
    median (full range (min-max))
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,7,8,5
    1.17 (1.08 to 1.62)
    1.22 (1.03 to 1.33)
    1.03 (0.93 to 1.08)
    1.08 (1.07 to 1.65)
    1.08 (1.07 to 1.57)
    1.18 (1.05 to 2.13)
    1.12 (1.00 to 1.68)
    1.08 (1.00 to 1.40)
    1.02 (0.97 to 1.20)
    1.17 (1.08 to 1.22)
    1.03 (1.00 to 1.13)
    1.12 (1.05 to 1.25)
    1.17 (1.03 to 1.25)
    1.11 (1.07 to 1.27)
    1.05 (1.02 to 1.17)
        C1D8:n=0,2,4,3,3,4,6,5,5,6,6,6,6,6,5
    99999 (99999 to 99999)
    1.19 (1.13 to 1.25)
    1.17 (1.07 to 2.08)
    1.03 (1.00 to 1.05)
    1.10 (1.03 to 1.42)
    1.09 (1.00 to 1.23)
    1.09 (1.03 to 1.13)
    1.13 (1.00 to 1.25)
    1.05 (1.00 to 1.17)
    1.05 (0.95 to 1.35)
    1.03 (1.00 to 1.12)
    1.12 (1.10 to 1.75)
    1.15 (0.98 to 3.08)
    1.08 (1.00 to 1.22)
    1.13 (1.08 to 1.17)
    No statistical analyses for this end point

    Secondary: Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981

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    End point title
    Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 [13]
    End point description
    AUC0-last for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    7
    8
    5
    Units: hours*nanograms per milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,7,8,5
    50.1 ( 35.0 )
    98.4 ( 15.5 )
    178 ( 19.6 )
    289 ( 40.6 )
    438 ( 34.5 )
    939 ( 20.7 )
    1070 ( 28.2 )
    1020 ( 25.8 )
    1310 ( 16.9 )
    1330 ( 15.7 )
    1460 ( 31.0 )
    1670 ( 31.9 )
    1410 ( 31.8 )
    2510 ( 30.1 )
    1890 ( 39.7 )
        C1D8:n=0,2,4,3,3,4,6,5,5,6,6,6,6,6,5
    99999 ( 99999 )
    98.6 ( 13.5 )
    174 ( 23.0 )
    364 ( 58.0 )
    405 ( 20.3 )
    1020 ( 31.1 )
    906 ( 30.6 )
    931 ( 19.5 )
    1220 ( 19.1 )
    1310 ( 33.0 )
    1230 ( 31.1 )
    1650 ( 47.6 )
    1300 ( 59.2 )
    3050 ( 81.2 )
    1620 ( 23.4 )
    No statistical analyses for this end point

    Secondary: Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981

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    End point title
    Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981 [14]
    End point description
    AUC0-inf for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only.Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    6
    7
    5
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,6,7,3
    53.5 ( 31.1 )
    100 ( 14.7 )
    181 ( 19.5 )
    294 ( 39.2 )
    443 ( 34.7 )
    949 ( 20.2 )
    1090 ( 28.0 )
    1040 ( 26.1 )
    1330 ( 17.0 )
    1350 ( 15.5 )
    1480 ( 31.6 )
    1700 ( 31.7 )
    1360 ( 32.3 )
    2540 ( 33.3 )
    2280 ( 5.6 )
        C1D8:n=0,2,4,3,3,4,5,5,4,6,6,6,5,5,5
    99999 ( 99999 )
    103 ( 12.8 )
    183 ( 21.9 )
    382 ( 53.5 )
    438 ( 16.2 )
    1050 ( 29.9 )
    897 ( 30.7 )
    967 ( 20.6 )
    1260 ( 21.9 )
    1410 ( 31.4 )
    1310 ( 28.3 )
    1710 ( 46.8 )
    1190 ( 40.8 )
    2590 ( 60.2 )
    1710 ( 24.4 )
    No statistical analyses for this end point

    Secondary: Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981

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    End point title
    Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 [15]
    End point description
    t1/2z for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    6
    7
    5
    Units: hours
    median (full range (min-max))
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,6,7,3
    5.41 (2.92 to 6.40)
    7.37 (4.90 to 9.90)
    7.60 (6.92 to 8.49)
    7.88 (5.81 to 10.32)
    7.87 (7.30 to 9.78)
    8.12 (6.77 to 9.19)
    9.18 (8.05 to 10.95)
    8.89 (6.56 to 11.81)
    9.44 (7.58 to 10.23)
    9.62 (7.30 to 10.48)
    8.01 (5.39 to 9.90)
    8.32 (7.06 to 13.77)
    8.38 (7.01 to 10.74)
    8.99 (7.38 to 11.67)
    8.61 (7.01 to 9.74)
        C1D8:n=0,2,4,3,3,4,5,5,4,6,6,6,5,5,5
    99999 (-99999 to 99999)
    5.74 (5.65 to 5.83)
    6.02 (4.53 to 6.74)
    6.08 (4.51 to 7.45)
    6.38 (6.12 to 10.33)
    5.73 (5.03 to 6.14)
    6.47 (5.15 to 6.59)
    6.16 (5.26 to 7.36)
    4.64 (3.12 to 6.81)
    2.95 (2.32 to 7.30)
    5.45 (3.02 to 6.13)
    6.54 (5.40 to 7.02)
    5.43 (3.00 to 6.20)
    6.20 (6.03 to 16.02)
    6.36 (3.12 to 7.16)
    No statistical analyses for this end point

    Secondary: Phase 1, CL: Total Clearance for TAK-981

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    End point title
    Phase 1, CL: Total Clearance for TAK-981 [16]
    End point description
    CL for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    6
    7
    5
    Units: liter per hour (L/h)
    geometric mean (geometric coefficient of variation)
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,6,7,3
    56.1 ( 31.1 )
    59.8 ( 14.7 )
    55.3 ( 19.5 )
    51.0 ( 39.2 )
    56.4 ( 34.7 )
    42.2 ( 20.2 )
    55.3 ( 28.0 )
    57.8 ( 26.1 )
    56.3 ( 17.0 )
    55.7 ( 15.5 )
    60.7 ( 31.6 )
    52.9 ( 31.7 )
    66.0 ( 32.3 )
    47.3 ( 33.3 )
    52.6 ( 5.6 )
        C1D8:n=0,2,4,3,3,4,5,5,4,6,6,6,5,5,5
    99999 ( 99999 )
    58.3 ( 12.8 )
    54.7 ( 21.9 )
    39.3 ( 53.5 )
    57.1 ( 16.2 )
    38.1 ( 29.9 )
    66.9 ( 30.7 )
    62.0 ( 20.6 )
    59.4 ( 21.9 )
    53.1 ( 31.4 )
    68.8 ( 28.3 )
    52.8 ( 46.8 )
    75.6 ( 40.8 )
    46.4 ( 60.2 )
    70.3 ( 24.4 )
    No statistical analyses for this end point

    Secondary: Phase 1, Vss: Volume of Distribution at Steady State for TAK-981

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    End point title
    Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 [17]
    End point description
    Vss for TAK-981 was reported. PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Here “number of subjects analyzed” "N" signifies participants who were evaluable for this endpoint and “number analyzed” signifies participants evaluable at specified time-points. As planned, this endpoint was analyzed in Phase 1 only. Here, “99999” indicates that no subjects were analyzed for Phase 1, Dose Escalation: TAK-981 3 mg BIW at Cycle 1 Day 8 because concentrations were below the lower limit of quantitation (LLOQ) after dosing. As planned, this endpoint was analyzed in Phase 1 only. Here “C” refers to cycle, “D” refers to day.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    7
    7
    6
    7
    5
    Units: liters
    geometric mean (geometric coefficient of variation)
        C1D1:n=5,3,4,3,4,4,7,6,6,6,7,7,6,7,3
    332 ( 37.9 )
    437 ( 18.2 )
    443 ( 28.9 )
    411 ( 72.8 )
    392 ( 39.9 )
    234 ( 36.0 )
    359 ( 33.5 )
    367 ( 19.2 )
    311 ( 24.0 )
    345 ( 29.1 )
    314 ( 46.3 )
    290 ( 59.4 )
    396 ( 25.8 )
    271 ( 31.3 )
    288 ( 27.6 )
        C1D8:n=0,2,4,3,3,4,5,5,4,6,6,6,5,5,5
    99999 ( 99999 )
    385 ( 12.9 )
    390 ( 32.0 )
    233 ( 119.7 )
    441 ( 41.0 )
    173 ( 51.7 )
    400 ( 32.2 )
    334 ( 21.2 )
    185 ( 48.8 )
    144 ( 84.8 )
    285 ( 39.3 )
    241 ( 76.2 )
    307 ( 60.6 )
    255 ( 36.6 )
    322 ( 32.7 )
    No statistical analyses for this end point

    Secondary: Phase 1: ORR

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    End point title
    Phase 1: ORR [18]
    End point description
    ORR was defined as percentage of participants who achieved CR or PR during the study as determined by the investigator according to response assessments based on RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 34.3 months)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    4
    3
    4
    3
    4
    3
    6
    6
    6
    6
    7
    6
    5
    7
    5
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.00 to 60.24)
    0.0 (0.00 to 70.76)
    0.0 (0.00 to 60.24)
    0.0 (0.00 to 70.76)
    0.0 (0.00 to 60.24)
    33.3 (0.84 to 90.57)
    0.0 (0.00 to 45.93)
    0.0 (0.00 to 45.93)
    0.0 (0.0 to 45.93)
    0.0 (0.0 to 45.93)
    0.0 (0.0 to 40.96)
    16.7 (0.42 to 64.12)
    0.0 (0.0 to 52.18)
    14.3 (0.36 to 57.87)
    0.0 (0.00 to 52.18)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Disease Control Rate (DCR)

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    End point title
    Phase 1 and 2: Disease Control Rate (DCR)
    End point description
    DCR was defined as the percentage of participants who achieved stable disease (SD) (greater than [>] 6 weeks) or better as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    4
    3
    4
    3
    4
    3
    6
    6
    6
    6
    7
    6
    5
    7
    5
    7
    3
    6
    4
    3
    1
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 60.24)
    0.0 (0.0 to 70.76)
    25.0 (0.63 to 80.59)
    33.3 (0.84 to 90.57)
    75.0 (19.41 to 99.37)
    66.7 (9.43 to 99.16)
    0.0 (0.0 to 45.93)
    66.7 (22.28 to 95.67)
    16.7 (0.42 to 64.12)
    66.7 (22.28 to 95.67)
    42.9 (9.90 to 81.59)
    50.0 (11.81 to 88.19)
    60.0 (14.66 to 94.73)
    42.9 (9.90 to 81.59)
    20.0 (0.51 to 71.64)
    71.4 (29.04 to 96.33)
    66.7 (9.43 to 99.16)
    33.3 (4.33 to 77.72)
    0.0 (0.0 to 60.24)
    0.0 (0.0 to 70.76)
    100.0 (2.50 to 100.0)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Duration of Response (DOR)

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    End point title
    Phase 1 and 2: Duration of Response (DOR)
    End point description
    DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR or better) and determined by the investigator according to RECIST v1.1 with solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Here, “number of subjects analyzed” signifies participants who had CR or PR and "99999" indicates median, upper or lower limit of 95% CI could not be estimated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From first documented confirmed CR or PR until first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    0 [23]
    1
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    1
    0 [29]
    1
    0 [30]
    0 [31]
    0 [32]
    0 [33]
    0 [34]
    0 [35]
    1
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    6.93 (-99999 to 99999)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    1.41 (-99999 to 99999)
    ( to )
    99999 (-99999 to 99999)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    5.55 (-99999 to 99999)
    Notes
    [19] - No participants with complete response or partial response were observed here.
    [20] - No participants with complete response or partial response were observed here.
    [21] - No participants with complete response or partial response were observed here.
    [22] - No participants with complete response or partial response were observed here.
    [23] - No participants with complete response or partial response were observed here.
    [24] - No participants with complete response or partial response were observed here.
    [25] - No participants with complete response or partial response were observed here.
    [26] - No participants with complete response or partial response were observed here.
    [27] - No participants with complete response or partial response were observed here.
    [28] - No participants with complete response or partial response were observed here.
    [29] - No participants with complete response or partial response were observed here.
    [30] - No participants with complete response or partial response were observed here.
    [31] - No participants with complete response or partial response were observed here.
    [32] - No participants with complete response or partial response were observed here.
    [33] - No participants with complete response or partial response were observed here.
    [34] - No participants with complete response or partial response were observed here.
    [35] - No participants with complete response or partial response were observed here.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Time to Progression (TTP)

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    End point title
    Phase 1 and 2: Time to Progression (TTP)
    End point description
    TTP was defined as the time from the date of the first dose administration to the date of first documented PD as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Here "99999" indicates median, upper or lower limit of 95% CI could not be estimated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to the date of the first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    7
    3
    7
    4
    3
    1
    Units: months
        median (confidence interval 95%)
    1.18 (0.72 to 99999)
    0.79 (0.76 to 99999)
    1.38 (0.59 to 99999)
    1.25 (1.18 to 99999)
    2.10 (1.38 to 99999)
    5.49 (1.25 to 99999)
    1.21 (0.46 to 99999)
    3.75 (0.72 to 99999)
    1.28 (1.22 to 99999)
    2.71 (1.35 to 8.08)
    6.97 (2.66 to 99999)
    3.94 (1.18 to 99999)
    2.79 (1.25 to 99999)
    99999 (1.38 to 99999)
    1.97 (1.74 to 2.04)
    6.06 (2.07 to 99999)
    3.78 (0.99 to 99999)
    1.18 (0.92 to 99999)
    1.04 (0.59 to 99999)
    1.09 (0.43 to 99999)
    11.17 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Time to Response (TTR)

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    End point title
    Phase 1 and 2: Time to Response (TTR)
    End point description
    TTR was defined as the time from the date of first study drug administration to the date of first documented PR or better by the investigator for responders according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Here, "number of subjects analyzed" "N" signifies participants who had CR or PR. Here "99999" indicates median, upper or lower limit of 95% CI could not be estimated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to the date of the first documentation of PR or better, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    0 [40]
    1
    0 [41]
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    1
    0 [46]
    1
    0 [47]
    0 [48]
    0 [49]
    0 [50]
    0 [51]
    0 [52]
    1
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    99999 (1.38 to 99999)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    99999 (3.91 to 99999)
    ( to )
    99999 (1.74 to 99999)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    5.65 (-99999 to 99999)
    Notes
    [36] - No participants with complete or partial response were observed here.
    [37] - No participants with complete or partial response were observed here.
    [38] - No participants with complete or partial response were observed here.
    [39] - No participants with complete or partial response were observed here.
    [40] - No participants with complete or partial response were observed here.
    [41] - No participants with complete or partial response were observed here.
    [42] - No participants with complete or partial response were observed here.
    [43] - No participants with complete or partial response were observed here.
    [44] - No participants with complete or partial response were observed here.
    [45] - No participants with complete or partial response were observed here.
    [46] - No participants with complete or partial response were observed here.
    [47] - No participants with complete or partial response were observed here.
    [48] - No participants with complete or partial response were observed here.
    [49] - No participants with complete or partial response were observed here.
    [50] - No participants with complete or partial response were observed here.
    [51] - No participants with complete or partial response were observed here.
    [52] - No participants with complete or partial response were observed here.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Progression-free Survival (PFS)

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    End point title
    Phase 1 and 2: Progression-free Survival (PFS)
    End point description
    PFS was defined as the time from the date of the first dose administration to the date of first documentation of PD or death due to any cause, whichever occurs first as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug. Here "99999" indicates upper or lower limit of 95% CI could not be estimated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug to date of PD or death, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    7
    3
    7
    4
    3
    1
    Units: months
        median (confidence interval 95%)
    0.95 (0.46 to 99999)
    0.79 (0.76 to 99999)
    1.38 (0.59 to 99999)
    1.25 (1.18 to 99999)
    2.10 (1.38 to 99999)
    5.49 (1.25 to 99999)
    1.18 (0.46 to 99999)
    2.53 (1.02 to 99999)
    1.27 (1.22 to 1.54)
    2.71 (1.35 to 8.08)
    2.66 (0.82 to 99999)
    3.94 (1.18 to 99999)
    2.79 (1.25 to 99999)
    3.32 (1.38 to 99999)
    1.97 (1.74 to 2.04)
    6.06 (2.07 to 99999)
    3.78 (0.99 to 99999)
    1.18 (0.92 to 99999)
    1.38 (0.59 to 99999)
    1.09 (0.43 to 99999)
    11.17 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Overall Survival (OS)

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    End point title
    Phase 1 and 2: Overall Survival (OS)
    End point description
    OS was defined as the time from the date of the first dose administration to the date of death. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug. Here, "99999" indicates median, upper limit or lower limit of 95% CI could not be estimated due to insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From date of first dose of study drug up to death up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    5
    3
    4
    3
    4
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    7
    3
    7
    4
    3
    1
    Units: months
        median (confidence interval 95%)
    99999 (0.46 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (3.02 to 99999)
    99999 (1.48 to 99999)
    99999 (1.25 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (0.82 to 99999)
    5.49 (5.49 to 99999)
    99999 (1.77 to 99999)
    99999 (5.22 to 99999)
    99999 (99999 to 99999)
    99999 (1.87 to 99999)
    99999 (3.29 to 99999)
    99999 (1.87 to 99999)
    2.43 (1.28 to 99999)
    6.14 (1.58 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 1: Fold Change from Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes

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    End point title
    Phase 1: Fold Change from Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes [53]
    End point description
    TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with antibody recognizing TAK-981-SUMO adduct formation during inhibition of SUMO-activating enzyme by TAK-981.Pharmacodynamic analysis set consisted of participants who provided evaluable blood samples(Cycle 1 Day 1 pre-dose sample and at least 1 post-dose sample).Here "number of subjects analyzed" "N" and number analyzed "n"= subjects evaluable for this endpoint at specified time-points, "99999" = no data as "n” was zero at specified time-points for specific arms.Cycle 1 Day 1,1 hour post-dose:n=3,3,4,3,3,4,7,6,6,6,8,7,7,8,6;Cycle 1 Day 1,4 hour post-dose:n=4,3,4,3,3,4,7,6,6,6,8,7,7,8,6;Cycle 1 Day 1,8 hour post-dose:n=4,3,4,3,3,4,7,5,6,6,8,7,7,8,6;Cycle 1 Day 8,Pre-dose:n=0,2,4,3,3,4,7,5,6,6,6,6,7,5,4;Cycle 1 Day 8,1 hour post-dose:n=0,2,4,3,3,4,6,5,6,6,6,6,7,4,4;Cycle 1 Day 8,4 hour post-dose:n=0,2,4,3,3,4,6,5,6,6,6,6,7,4,5;Cycle 1 Day 8,8 hour post-dose:n=0,2,4,3,3,4,6,4,6,6,6,6,6,4,5.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days)
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    4
    3
    4
    3
    3
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    Units: fold change
    arithmetic mean (standard deviation)
        Cycle 1 Day 1: 1 hour post-dose
    1.8 ( 0.21 )
    2.3 ( 0.16 )
    2.9 ( 1.38 )
    5.9 ( 0.83 )
    5.9 ( 1.07 )
    8.4 ( 1.25 )
    7.5 ( 2.57 )
    6.5 ( 2.27 )
    7.8 ( 1.59 )
    7.0 ( 2.03 )
    8.5 ( 1.10 )
    8.8 ( 1.46 )
    8.1 ( 2.12 )
    8.5 ( 2.12 )
    8.1 ( 1.41 )
        Cycle 1 Day 1: 4 hour post-dose
    1.6 ( 0.19 )
    2.1 ( 0.04 )
    2.6 ( 1.64 )
    4.8 ( 0.70 )
    5.1 ( 0.74 )
    5.8 ( 0.44 )
    6.2 ( 2.15 )
    4.7 ( 1.57 )
    5.8 ( 0.86 )
    5.8 ( 1.05 )
    6.0 ( 1.05 )
    6.2 ( 1.10 )
    5.9 ( 1.42 )
    6.2 ( 1.32 )
    5.8 ( 1.22 )
        Cycle 1 Day 1: 8 hour post-dose
    1.5 ( 0.23 )
    1.9 ( 0.08 )
    2.7 ( 1.36 )
    4.3 ( 0.85 )
    4.6 ( 0.77 )
    4.9 ( 0.10 )
    4.3 ( 2.05 )
    3.3 ( 1.02 )
    5.2 ( 1.49 )
    4.8 ( 1.10 )
    4.7 ( 1.02 )
    5.5 ( 1.32 )
    4.9 ( 1.20 )
    5.0 ( 0.94 )
    4.0 ( 1.21 )
        Cycle 1 Day 8: Pre-dose
    99999 ( 99999 )
    1.8 ( 0.27 )
    2.0 ( 0.80 )
    3.6 ( 0.92 )
    3.3 ( 0.31 )
    2.9 ( 0.87 )
    2.9 ( 1.20 )
    2.1 ( 0.30 )
    3.9 ( 0.75 )
    2.1 ( 0.66 )
    2.6 ( 0.92 )
    2.4 ( 0.53 )
    2.4 ( 0.62 )
    3.7 ( 1.06 )
    2.3 ( 0.38 )
        Cycle 1 Day 8: 1 hour post-dose
    99999 ( 99999 )
    3.2 ( 0.72 )
    3.8 ( 1.73 )
    8.0 ( 3.03 )
    7.9 ( 2.00 )
    8.4 ( 2.20 )
    9.6 ( 3.94 )
    6.9 ( 0.89 )
    8.7 ( 2.91 )
    7.4 ( 2.95 )
    7.5 ( 2.18 )
    9.6 ( 1.74 )
    8.4 ( 2.68 )
    9.2 ( 1.79 )
    8.2 ( 1.94 )
        Cycle 1 Day 8: 4 hour post-dose
    99999 ( 99999 )
    2.9 ( 0.62 )
    3.4 ( 1.55 )
    7.1 ( 2.38 )
    7.2 ( 1.84 )
    6.3 ( 2.01 )
    7.3 ( 3.17 )
    5.3 ( 0.55 )
    7.1 ( 1.47 )
    5.9 ( 2.37 )
    6.9 ( 0.85 )
    6.9 ( 1.58 )
    6.2 ( 1.81 )
    7.9 ( 1.90 )
    6.1 ( 1.30 )
        Cycle 1 Day 8: 8 hour post-dose
    99999 ( 99999 )
    2.9 ( 0.65 )
    3.2 ( 1.53 )
    6.7 ( 1.98 )
    6.0 ( 1.42 )
    6.1 ( 2.45 )
    6.3 ( 2.63 )
    4.3 ( 0.59 )
    6.6 ( 1.68 )
    5.2 ( 2.05 )
    5.8 ( 1.19 )
    5.7 ( 1.05 )
    5.8 ( 2.04 )
    5.9 ( 0.83 )
    5.2 ( 1.06 )
    No statistical analyses for this end point

    Secondary: Phase 1: Fold Change from Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin

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    End point title
    Phase 1: Fold Change from Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin [54]
    End point description
    TAK-981-SUMO adduct formation in skin was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981. Pharmacodynamic analysis set consisted of participants who provided evaluable skin biopsies (screening sample and at least 1 on-treatment sample). Here "number of subjects analyzed" "N" signifies participants who were evaluable for this endpoint. Here "99999" indicates standard deviation could not be estimated due to insufficient number of participants available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 8 (Cycle length = 21 days)
    Notes
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    0 [55]
    0 [56]
    1
    0 [57]
    0 [58]
    0 [59]
    0 [60]
    0 [61]
    0 [62]
    0 [63]
    0 [64]
    1
    0 [65]
    0 [66]
    0 [67]
    Units: fold change
    arithmetic mean (standard deviation)
        Cycle 1 Day 8
    ( )
    ( )
    115.57 ( 99999 )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    1343.23 ( 99999 )
    ( )
    ( )
    ( )
    Notes
    [55] - No participants were observed in this arm.
    [56] - No participants were observed in this arm.
    [57] - No participants were observed in this arm.
    [58] - No participants were observed in this arm.
    [59] - No participants were observed in this arm.
    [60] - No participants were observed in this arm.
    [61] - No participants were observed in this arm.
    [62] - No participants were observed in this arm.
    [63] - No participants were observed in this arm.
    [64] - No participants were observed in this arm.
    [65] - No participants were observed in this arm.
    [66] - No participants were observed in this arm.
    [67] - No participants were observed in this arm.
    No statistical analyses for this end point

    Secondary: Phase 1: Fold Change from Baseline in SUMO Pathway Inhibition in Blood Lymphocytes

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    End point title
    Phase 1: Fold Change from Baseline in SUMO Pathway Inhibition in Blood Lymphocytes [68]
    End point description
    SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with antibody recognizing SUMO-2/3 chains. Pharmacodynamic analysis set consisted of participants who provided evaluable blood samples (Cycle 1 Day 1 pre-dose sample and at least 1 post-dose sample). Here "number of subjects analyzed" "N" signifies participants who were evaluable for this endpoint, number analyzed "n" signifies subjects evaluable at specified time-points, "99999" indicates no data was available as "n” was zero at specified time-points for specific arms.Cycle 1 Day 1,1 hour post-dose:n=3,3,4,3,3,4,7,6,6,6,8,7,7,8,6; Cycle 1 Day 1,4 hour post-dose:n=4,3,4,3,3,4,7,6,6,6,8,7,7,8,6;Cycle 1 Day 1,8 hour post-dose:n=4,3,4,3,3,4,7,5,6,6,8,7,7,8,6;Cycle 1 Day 8,Pre-dose:n=0,2,4,3,3,4,7,5,6,6,6,6,7,5,4;Cycle 1 Day 8,1 hour post-dose:n =0,2,4,3,3,4,6,5,6,6,6,6,7,4,4;Cycle 1 Day 8,4 hour post-dose:n=0,2,4,3,3,4,6,5,6,6,6,6,7,4,5;Cycle 1 Day 8,8 hour post-dose:n=0,2,4,3,3,4,6,4,6,6,6,6,6,4,5..
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days)
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    4
    3
    4
    3
    3
    4
    7
    6
    6
    6
    8
    7
    7
    8
    6
    Units: fold change
    arithmetic mean (standard deviation)
        Cycle 1 Day 1: 1 hour post-dose
    1.0 ( 0.04 )
    1.0 ( 0.05 )
    0.9 ( 0.11 )
    0.9 ( 0.04 )
    0.9 ( 0.06 )
    4.7 ( 7.88 )
    0.8 ( 0.13 )
    0.7 ( 0.13 )
    0.6 ( 0.14 )
    0.6 ( 0.11 )
    0.6 ( 0.11 )
    0.6 ( 0.12 )
    0.6 ( 0.09 )
    0.5 ( 0.07 )
    0.6 ( 0.22 )
        Cycle 1 Day 1: 4 hour post-dose
    0.9 ( 0.15 )
    1.0 ( 0.07 )
    1.0 ( 0.07 )
    0.9 ( 0.05 )
    1.0 ( 0.09 )
    4.1 ( 6.38 )
    2.3 ( 4.03 )
    0.9 ( 0.41 )
    0.5 ( 0.20 )
    2.5 ( 4.74 )
    0.6 ( 0.13 )
    0.6 ( 0.18 )
    0.6 ( 0.11 )
    0.5 ( 0.14 )
    0.6 ( 0.36 )
        Cycle 1 Day 1: 8 hour post-dose
    1.0 ( 0.20 )
    1.0 ( 0.12 )
    1.0 ( 0.19 )
    1.0 ( 0.07 )
    0.9 ( 0.18 )
    4.0 ( 6.19 )
    0.7 ( 0.18 )
    0.7 ( 0.25 )
    0.6 ( 0.26 )
    2.5 ( 4.49 )
    0.6 ( 0.17 )
    0.7 ( 0.13 )
    0.6 ( 0.11 )
    0.6 ( 0.23 )
    0.6 ( 0.35 )
        Cycle 1 Day 8: Pre-dose
    99999 ( 99999 )
    1.0 ( 0.17 )
    1.0 ( 0.15 )
    1.1 ( 0.16 )
    1.7 ( 0.82 )
    5.5 ( 9.42 )
    2.1 ( 3.57 )
    1.5 ( 0.66 )
    1.0 ( 0.24 )
    1.0 ( 0.16 )
    0.8 ( 0.43 )
    1.1 ( 0.27 )
    1.0 ( 0.18 )
    1.1 ( 0.21 )
    2.8 ( 3.74 )
        Cycle 1 Day 8: 1 hour post-dose
    99999 ( 99999 )
    1.0 ( 0.16 )
    1.0 ( 0.14 )
    0.9 ( 0.10 )
    1.6 ( 0.68 )
    4.6 ( 8.08 )
    0.6 ( 0.35 )
    0.9 ( 0.41 )
    0.5 ( 0.24 )
    0.6 ( 0.22 )
    0.5 ( 0.23 )
    0.7 ( 0.19 )
    0.5 ( 0.09 )
    0.6 ( 0.17 )
    1.5 ( 2.00 )
        Cycle 1 Day 8: 4 hour post-dose
    99999 ( 99999 )
    1.0 ( 0.15 )
    1.0 ( 0.15 )
    1.0 ( 0.08 )
    1.7 ( 0.77 )
    4.6 ( 7.98 )
    0.7 ( 0.31 )
    1.0 ( 0.51 )
    0.6 ( 0.22 )
    1.8 ( 3.05 )
    0.7 ( 0.16 )
    0.7 ( 0.19 )
    0.6 ( 0.14 )
    0.7 ( 0.19 )
    1.5 ( 1.87 )
        Cycle 1 Day 8: 8 hour post-dose
    99999 ( 99999 )
    1.1 ( 0.10 )
    1.0 ( 0.23 )
    0.9 ( 0.11 )
    1.7 ( 0.65 )
    4.6 ( 8.20 )
    0.7 ( 0.30 )
    1.0 ( 0.76 )
    0.6 ( 0.18 )
    1.9 ( 3.06 )
    0.8 ( 0.19 )
    0.7 ( 0.20 )
    0.6 ( 0.21 )
    0.6 ( 0.18 )
    1.5 ( 2.14 )
    No statistical analyses for this end point

    Secondary: Phase 1: Fold Change from Baseline in SUMO Pathway Inhibition in Skin

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    End point title
    Phase 1: Fold Change from Baseline in SUMO Pathway Inhibition in Skin [69]
    End point description
    SUMO pathway inhibition in skin was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains. Pharmacodynamic analysis set consisted of participants who provided evaluable skin biopsies (screening sample and at least 1 on-treatment sample). Here "number of subjects analyzed" "N” signifies participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 8 (Cycle length = 21 days)
    Notes
    [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 1, Dose Escalation: TAK-981 3 mg BIW Phase 1, Dose Escalation: TAK-981 6 mg BIW Phase 1, Dose Escalation: TAK-981 10 mg BIW Phase 1, Dose Escalation: TAK-981 15 mg BIW Phase 1, Dose Escalation: TAK-981 25 mg BIW Phase 1, Dose Escalation: TAK-981 40 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg BIW Phase 1, Dose Escalation: TAK-981 60 mg QW Phase 1, Dose Escalation: TAK-981 75 mg BIW Phase 1, Dose Escalation: TAK-981 75 mg QW Phase 1, Dose Escalation: TAK-981 90 mg BIW Phase 1, Dose Escalation: TAK-981 90 mg QW Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Phase 1, Dose Escalation: TAK-981 120 mg BIW Phase 1, Dose Escalation: TAK-981 120 mg QW
    Number of subjects analysed
    3
    3
    4
    3
    4
    4
    5
    5
    6
    6
    6
    6
    6
    6
    6
    Units: fold change
    arithmetic mean (standard deviation)
        Cycle 1 Day 8
    1.01 ( 0.067 )
    0.71 ( 0.398 )
    0.82 ( 0.088 )
    0.91 ( 0.233 )
    1.05 ( 0.122 )
    0.86 ( 0.146 )
    0.72 ( 0.276 )
    0.73 ( 0.298 )
    0.64 ( 0.156 )
    0.71 ( 0.224 )
    0.56 ( 0.136 )
    0.65 ( 0.298 )
    0.78 ( 0.123 )
    0.42 ( 0.376 )
    0.44 ( 0.210 )
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants Reporting one or More TEAEs

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    End point title
    Phase 2: Number of Participants Reporting one or More TEAEs [70]
    End point description
    TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. Any abnormal laboratory results were considered as TEAEs. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
    Notes
    [70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    7
    3
    7
    4
    3
    1
    Units: participants
    6
    3
    7
    4
    3
    1
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants With Grade 3 or Higher TEAEs

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    End point title
    Phase 2: Number of Participants With Grade 3 or Higher TEAEs [71]
    End point description
    The severity grade was evaluated as per the CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
    Notes
    [71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    7
    3
    7
    4
    3
    1
    Units: participants
    4
    1
    6
    3
    3
    1
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of TEAEs

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    End point title
    Phase 2: Duration of TEAEs [72]
    End point description
    TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
    Notes
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Number of subjects analysed
    7
    3
    7
    4
    3
    1
    Units: days
        median (full range (min-max))
    8.5 (1 to 336)
    4.0 (1 to 45)
    5.0 (1 to 72)
    5.0 (1 to 26)
    3.0 (1 to 19)
    1.0 (1 to 56)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious/Non-serious AEs: From first dose of study drug to 30 days after last dose up to 35.3 months (Phase 1) up to 12.2 months (Phase 2); All fatalities: From first dose up to death due to any cause up to 34.3 months (Phase 1) up to 12.2 months (Phase 2)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Phase 1: TAK-981 25mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 25 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 15mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 15 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 10mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 10 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 6mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 6 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 3mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 3 milligram (mg), infusion, intravenously, twice weekly (BIW) on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 75mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 75mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 60mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, once weekly (QW) on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 60mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 40mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 40 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 90mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW
    Reporting group description
    Participants with microsatellite-stable colorectal cancer (MSS-CRC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW
    Reporting group description
    Participants with cervical cancer received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 90mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 90mg Days 1,8,15
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1, 8 and 15 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 120mg BIW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 1: TAK-981 120mg QW
    Reporting group description
    Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW
    Reporting group description
    Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) progressed or relapsed after chimeric antigen receptor (CAR) T-cell therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory DLBCL that have not received prior cellular therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Reporting group title
    Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Reporting group description
    Participants with relapsed/refractory follicular lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred.

    Serious adverse events
    Phase 1: TAK-981 25mg BIW Phase 1: TAK-981 15mg BIW Phase 1: TAK-981 10mg BIW Phase 1: TAK-981 6mg BIW Phase 1: TAK-981 3mg BIW Phase 1: TAK-981 75mg QW Phase 1: TAK-981 75mg BIW Phase 1: TAK-981 60mg QW Phase 1: TAK-981 60mg BIW Phase 1: TAK-981 40mg BIW Phase 1: TAK-981 90mg BIW Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW Phase 1: TAK-981 90mg QW Phase 1: TAK-981 90mg Days 1,8,15 Phase 1: TAK-981 120mg BIW Phase 1: TAK-981 120mg QW Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 4 (75.00%)
    2 / 3 (66.67%)
    3 / 5 (60.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
    3 / 7 (42.86%)
    2 / 4 (50.00%)
    5 / 8 (62.50%)
    4 / 7 (57.14%)
    1 / 3 (33.33%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    5 / 8 (62.50%)
    2 / 6 (33.33%)
    2 / 7 (28.57%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
         number of deaths (all causes)
    1
    0
    0
    0
    1
    0
    1
    1
    2
    1
    2
    1
    1
    2
    1
    1
    0
    1
    4
    2
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    1
    0
    1
    1
    2
    1
    2
    1
    0
    0
    1
    1
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    2 / 7 (28.57%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cognitive disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness postural
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glossodynia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal mass
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal obstruction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
    0 / 4 (0.00%)