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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

TAK-981-1002

ISRCTN number

US NCT number

NCT03648372

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Dec 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Dec 2023

Was the trial ended prematurely?

Yes

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

Independent data monitoring committee (IDMC) involvement?

Yes

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

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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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.

Screening details

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

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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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Reporting group title

Phase 1, Dose Escalation: TAK-981 3 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 6 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 10 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 15 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 25 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 40 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 60 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 60 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 75 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 75 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 120 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 120 mg QW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW

Reporting group description

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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Reporting group title

Phase 1, Dose Escalation: TAK-981 3 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 6 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 10 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 15 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 25 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 40 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 60 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 60 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 75 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 75 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg QW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 120 mg BIW

Reporting group description

Reporting group title

Phase 1, Dose Escalation: TAK-981 120 mg QW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW

Reporting group description

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.

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

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.

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

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: hoursnanograms per milliliter (hng/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.

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

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.

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

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 (0.0 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)

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

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)

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]

0 ^[24]

0 ^[25]

0 ^[26]

0 ^[27]

0 ^[28]

0 ^[29]

0 ^[30]

0 ^[31]

0 ^[32]

0 ^[33]

0 ^[34]

0 ^[35]

Units: months

median (confidence interval 95%)

( to )

6.93 (-99999 to 99999)

( to )

1.41 (-99999 to 99999)

( to )

99999 (-99999 to 99999)

( 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)

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

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)

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]

0 ^[41]

0 ^[42]

0 ^[43]

0 ^[44]

0 ^[45]

0 ^[46]

0 ^[47]

0 ^[48]

0 ^[49]

0 ^[50]

0 ^[51]

0 ^[52]

Units: months

median (confidence interval 95%)

( to )

99999 (1.38 to 99999)

( to )

99999 (3.91 to 99999)

( to )

99999 (1.74 to 99999)

( 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)

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

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)

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

Units: months

median (confidence interval 95%)

99999 (0.46 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 (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.

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]

0 ^[57]

0 ^[58]

0 ^[59]

0 ^[60]

0 ^[61]

0 ^[62]

0 ^[63]

0 ^[64]

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

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

Top of page

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 name

MedDRA

Dictionary version

26.1

Reporting group title

Phase 1: TAK-981 25mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 15mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 10mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 6mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 3mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 75mg QW

Reporting group description

Reporting group title

Phase 1: TAK-981 75mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 60mg QW

Reporting group description

Reporting group title

Phase 1: TAK-981 60mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 40mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 90mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort C: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort B: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 90mg QW

Reporting group description

Reporting group title

Phase 1: TAK-981 90mg Days 1,8,15

Reporting group description

Reporting group title

Phase 1: TAK-981 120mg BIW

Reporting group description

Reporting group title

Phase 1: TAK-981 120mg QW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort A: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort D: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort E: TAK-981 90 mg BIW

Reporting group description

Reporting group title

Phase 2, Dose Expansion, Cohort F: TAK-981 90 mg BIW

Reporting group description

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%)

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)

number of deaths resulting from adverse events

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 / 7 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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%)

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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%)

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 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 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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%)

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 / 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

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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%)

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 / 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

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

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%)

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 3 (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

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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%)

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 / 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

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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

1 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

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 / 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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

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%)

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 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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

deaths causally related to treatment / all

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%)

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 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (0.00%)

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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

1 / 3 (33.33%)

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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 3 (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 / 1

0 / 0

deaths causally related to treatment / all

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 / 7 (0.00%)

0 / 4 (0.00%)

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

Primary: Phase 1: Duration of TEAEs

Primary: Phase 1: Duration of TEAEs

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

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

Primary: Phase 2: Overall Response Rate (ORR)

Primary: Phase 2: Overall Response Rate (ORR)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Phase 1: ORR

Secondary: Phase 1: ORR

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Phase 2: Duration of TEAEs

Secondary: Phase 2: Duration of TEAEs

Adverse events

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