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    Clinical Trial Results:
    A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) with or without Durvalumab in Combination with Chemotherapy in Subjects with Metastatic Pancreatic Ductal Adenocarcinoma

    Summary
    EudraCT number
    		 2018-001028-21
    Trial protocol
    		 NO   ES  
    Global end of trial date
    22 Jul 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    24 Sep 2023
    First version publication date
    03 Aug 2023
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D6070C00005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03611556
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, Maryland, United States, 20878
    Public contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Nov 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study are: 1. To assess the safety and tolerability of oleclumab (Ole) plus durvalumab (Durva) in combination with chemotherapy administered in participants with metastatic pancreatic ductal adenocarcinoma (PDAC) in dose escalation phase (Part 1). 2. To evaluate the preliminary antitumor activity of ole with or without durva in combination with gemcitabine (Gem) and nab-paclitaxel (nab-pacli) compared to gem and nab-pacli administered in participants with first-line metastatic PDAC in dose expansion phase (Part 2). 3. To evaluate the preliminary antitumor activity of ole with or without durva in combination with modified regimen of leucovorin (folinic acid), 5-fluorouracil, and oxaliplatin (mFOLFOX) compared to mFOLFOX administered in participants with second-line (2L) metastatic PDAC in dose expansion phase (Part 2).
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Norway: 4
    Country: Number of subjects enrolled
    Spain: 24
    Country: Number of subjects enrolled
    United States: 146
    Worldwide total number of subjects
    195
    EEA total number of subjects
    28
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    102
    From 65 to 84 years
    92
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 29 sites in 4 countries (Australia, Norway, Spain, and the United States of America).

    Pre-assignment
    Screening details
    		 A total of 25 participants were treated in dose escalation part of this study. A total of 188 participants were randomized in dose expansion part of this study of which 170 participants were treated (18 participants were randomized but not treated). Results are presented for 195 treated participants only.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) until disease progression (PD), intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Arm description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    mFOLFOX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Arm description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    mFOLFOX
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Arm title
    		 Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Arm description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oleclumab
    Investigational medicinal product code
    Other name
    MEDI9447
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of nab-paclitaxel 125 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of gemcitabine 1000 mg/m^2 on Days 1, 8, and 15 and then repeated on Q4W schedule until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    MEDI4736
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous infusion of durvalumab 1500 mg Q4W until PD, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Number of subjects in period 1
    		Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Started
    7
    7
    3
    8
    62
    38
    70
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    7
    7
    3
    8
    62
    38
    70
         Adverse event, serious fatal
    1
    -
    -
    -
    3
    1
    3
         Death due to disease progression
    6
    7
    3
    8
    42
    31
    49
         Death due to toxicity related to study drug
    -
    -
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    -
    -
    -
    -
    4
    2
    4
         Death, reason unspecified
    -
    -
    -
    -
    2
    -
    -
         Sponsor decision
    -
    -
    -
    -
    9
    4
    12
         Reasons
    -
    -
    -
    -
    2
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli Total
    Number of subjects
    		 7 7 3 8 62 38 70 195
    Age categorical
    Units: Participants
        In utero
    		 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 2 4 1 3 29 23 40 102
        From 65-84 years
    		 5 3 2 5 32 15 30 92
        85 years and over
    		 0 0 0 0 1 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 66.7 ( 12.8 ) 59.6 ( 11.4 ) 67.0 ( 14.9 ) 64.8 ( 4.8 ) 65.6 ( 8.0 ) 62.5 ( 11.1 ) 62.9 ( 8.3 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 3 4 1 4 26 17 34 89
        Male
    		 4 3 2 4 36 21 36 106
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 1 1
        Asian
    		 0 0 0 0 5 1 1 7
        Native Hawaiian or Other Pacific Islander
    		 1 0 0 0 0 0 0 1
        Black or African American
    		 0 1 0 2 3 2 2 10
        White
    		 6 5 3 6 54 33 64 171
        More than one race
    		 0 1 0 0 0 1 0 2
        Unknown or Not Reported
    		 0 0 0 0 0 1 2 3
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 1 0 1 1 3
        Not Hispanic or Latino
    		 7 7 3 7 61 37 69 191
        Unknown or Not Reported
    		 0 0 0 0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with first-line (1L) metastatic disease received intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; fluorouracil [5-FU] 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 Participants with 2L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 Participants with 1L metastatic disease received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and high CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Subject analysis set title
    Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In dose-expansion phase, participants with 1L metastatic disease and low CD73 levels received IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase [1] [2]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Any TEAEs
    7
    7
    3
    8
        Any TESAEs
    4
    6
    0
    4
    No statistical analyses for this end point

    Primary: Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase

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    End point title
    		 Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase [3] [4]
    End point description
    DLT: Any study drug related Grade (G)3/higher toxicity including: any G4 immune-mediated AEs,>=G3 colitis/pneumonitis(PN)/interstitial lung disease (ILD),>=G3 nausea/vomiting/diarrhea that did not resolve to G2/less in 3 days of maximal supportive care (MSC), G2 PN/ILD that did not resolve in 7 days of starting MSC, G4 anemia, G3 anemia with clinical sequelae/>2 units of red blood cells transfusion, G4 thrombocytopenia(TP)/neutropenia>=7 days, G3/4 TP with >=G3 hemorrhage, G4 febrile neutropenia(FN), G3 FN >=5 days with MSC, isolated G3; liver transaminase elevation(LTE)/total bilirubin(TBL) that did not downgrade to G1/less in 14 days of onset, isolated G4 LTE/TBL, AST/ALT >3×upper limit normal (ULN) and concurrent TBL >2×ULN, any other toxicity judged by Dose Escalation Committee. The DLT-evaluable population included all participants who received planned doses of study drugs in dose-escalation phase and completed safety follow-up/experienced any DLT during DLT-evaluation period.
    End point type
    Primary
    End point timeframe
    From Day 1 to 28 days after the first dose of study drugs
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    5
    6
    3
    8
    Units: Participants
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase [5] [6]
    End point description
    Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Pyrexia
    3
    3
    0
    1
        Dyspnoea
    1
    0
    0
    0
        Dyspnoea exertional
    0
    1
    0
    0
        Hypotension
    2
    1
    0
    1
        Temperature intolerance
    0
    0
    1
    0
        Hypertension
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase

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    End point title
    		 Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase [7] [8]
    End point description
    Number of participants with abnormal ECG parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Atrial fibrillation
    0
    1
    0
    0
        Tachycardia
    0
    1
    0
    0
        Atrioventricular block
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase

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    End point title
    		 Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase [9] [10]
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Primary
    End point timeframe
    Day 1 through 65.7 weeks (maximum observed duration)
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Participants
        Anaemia
    3
    3
    1
    0
        Neutropenia
    2
    2
    2
    1
        Thrombocytopenia
    2
    2
    2
    1
        Hypothyroidism
    0
    1
    0
    1
        Alanine aminotransferase increased
    3
    4
    0
    2
        Aspartate aminotransferase increased
    3
    3
    0
    3
        Blood alkaline phosphatase increased
    2
    1
    0
    1
        Blood bilirubin increased
    1
    0
    0
    1
        Blood creatinine increased
    0
    3
    0
    0
        Blood glucose decreased
    1
    0
    0
    0
        International normalised ratio increased
    1
    0
    0
    0
        Lymphocyte count decreased
    0
    1
    0
    2
        Neutrophil count decreased
    0
    2
    1
    3
        Platelet count decreased
    1
    3
    1
    2
        White blood cell count decreased
    0
    2
    0
    2
        Hypoalbuminaemia
    0
    2
    0
    1
        Hypocalcaemia
    0
    1
    0
    1
        Hypokalaemia
    0
    3
    0
    2
        Hypomagnesaemia
    1
    2
    0
    1
        Hyponatraemia
    0
    2
    0
    2
        Hypophosphataemia
    0
    1
    0
    0
        Proteinuria
    1
    0
    0
    0
        Hyperthyroidism
    0
    0
    0
    1
        Amylase increased
    0
    0
    1
    1
        Gamma-glutamyltransferase increased
    0
    0
    0
    1
        Lipase increased
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose Expansion Phase

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    End point title
    		 Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose Expansion Phase [11]
    End point description
    The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), any pathological lymph nodes (LN) (target [TLN] and non-target [NTLN]) must have reduction in short axis <10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. The intent-to treat (ITT) population included all participants who were randomized and received any study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Primary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Percentage of Participants
        number (confidence interval 95%)
    29.0 (18.2 to 41.9)
    21.1 (9.6 to 37.3)
    32.9 (22.1 to 45.1)
    Statistical analysis title
    		 Statistical Analysis 1 (a)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3614 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    -8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.6
         upper limit
    		 12.1
    Notes
    [12] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 2 (a)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6503 [13]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.2
         upper limit
    		 20.7
    Notes
    [13] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 2 (b)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6503 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    3.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 15
    Notes
    [14] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.
    Statistical analysis title
    		 Statistical Analysis 1 (b)
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3614 [15]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    -8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -20.9
         upper limit
    		 5.2
    Notes
    [15] - Nominal P-value for comparison of treatment groups obtained from Cochran-Mantel-Haenszel-test was stratified by CD73 level.

    Secondary: Number of Participants With TEAEs and TESAEs in Dose Expansion Phase

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    End point title
    		 Number of Participants With TEAEs and TESAEs in Dose Expansion Phase [16]
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Any TEAEs
    62
    37
    70
        Any TESAEs
    34
    24
    37
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase [17]
    End point description
    Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Hypothermia
    0
    0
    1
        Pyrexia
    15
    12
    21
        Dyspnoea
    7
    6
    8
        Dyspnoea exertional
    1
    1
    2
        Hypertension
    2
    3
    11
        Hypotension
    3
    4
    4
        Orthostatic hypotension
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase

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    End point title
    		 Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase [18]
    End point description
    Number of participants with abnormal ECG parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Supraventricular tachycardia
    0
    1
    0
        Tachycardia
    2
    3
    3
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase

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    End point title
    		 Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase [19]
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (maximum observed duration)
    Notes
    [19] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants
        Anaemia
    17
    14
    28
        Febrile neutropenia
    0
    1
    3
        Leukocytosis
    1
    0
    1
        Leukopenia
    1
    2
    3
        Lymphopenia
    2
    0
    2
        Neutropenia
    22
    15
    16
        Thrombocytopenia
    6
    7
    13
        Thrombocytosis
    2
    0
    1
        Hyperthyroidism
    0
    0
    3
        Hypothyroidism
    0
    0
    7
        Hypertransaminasaemia
    0
    1
    0
        Alanine aminotransferase decreased
    1
    0
    0
        Alanine aminotransferase increased
    8
    9
    16
        Amylase increased
    1
    0
    1
        Aspartate aminotransferase increased
    11
    8
    15
        Blood albumin decreased
    1
    0
    0
        Blood alkaline phosphatase increased
    3
    2
    8
        Blood bilirubin increased
    3
    3
    2
        Blood creatinine increased
    2
    0
    8
        Blood glucose increased
    0
    2
    0
        Blood lactate dehydrogenase increased
    1
    0
    3
        Blood magnesium decreased
    0
    1
    0
        Blood oestrogen decreased
    0
    1
    0
        Gamma-glutamyltransferase increased
    6
    1
    8
        Haemoglobin decreased
    0
    0
    1
        International normalised ratio increased
    0
    0
    1
        Lipase increased
    0
    1
    2
        Liver function test increased
    1
    0
    0
        Lymphocyte count decreased
    4
    2
    6
        Neutrophil count
    0
    0
    1
        Neutrophil count decreased
    19
    8
    24
        Platelet count decreased
    13
    9
    20
        Troponin I increased
    1
    0
    0
        White blood cell count decreased
    6
    6
    10
        White blood cell count increased
    0
    1
    0
        Hyperglycaemia
    4
    2
    6
        Hyperkalaemia
    1
    1
    1
        Hypoalbuminaemia
    3
    2
    6
        Hypocalcaemia
    2
    2
    3
        Hypoglycaemia
    0
    0
    2
        Hypokalaemia
    4
    2
    8
        Hypomagnesaemia
    4
    3
    6
        Hyponatraemia
    8
    0
    3
        Hypophosphataemia
    1
    0
    0
        Hypovolaemia
    1
    0
    0
        Iron deficiency
    0
    0
    1
        Type 2 diabetes mellitus
    0
    1
    0
        Proteinuria
    0
    1
    1
    No statistical analyses for this end point

    Secondary: Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase

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    End point title
    		 Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase [20]
    End point description
    The OR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. The numbers of confidence interval (CI) '0 to 0' signified that there was zero responder in the specified cohort, so 95% CI could not be calculated.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
    Notes
    [20] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Percentage of Participants
        number (confidence interval 95%)
    0 (0 to 0)
    14.3 (0.4 to 57.9)
    0 (0 to 0)
    12.5 (0.3 to 52.7)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase

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    End point title
    		 Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase [21]
    End point description
    DC: defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis <10 mm, and no new lesions. The PR is at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from first documentation date. The SD is neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for progressive disease (PD), and no new lesions. The PD is at least 20% increase in SoD of TLs and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
    Notes
    [21] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Number of subjects analysed
    7
    7
    3
    8
    Units: Percentage of Participants
        number (confidence interval 95%)
    42.9 (9.9 to 81.6)
    71.4 (29.0 to 96.3)
    66.7 (9.4 to 99.2)
    62.5 (24.5 to 91.5)
    No statistical analyses for this end point

    Secondary: Number of Participants With Overall Survival Events in Dose Expansion Phase

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    End point title
    		 Number of Participants With Overall Survival Events in Dose Expansion Phase [22]
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. The number of participants with overall survival events (deaths) is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    Notes
    [22] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants with event
        number (not applicable)
    47
    32
    53
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.498
         upper limit
    		 1.131
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.983

    Secondary: Overall Survival in Dose Expansion Phase

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    End point title
    		 Overall Survival in Dose Expansion Phase [23]
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    Notes
    [23] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Months
        median (confidence interval 95%)
    10.8 (8.2 to 13.2)
    8.9 (6.9 to 11.5)
    12.9 (10.1 to 15.3)
    No statistical analyses for this end point

    Secondary: Number of Participants With Progression-free Survival (PFS) Events According to RECIST v1.1 in Dose Expansion Phase

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    End point title
    		 Number of Participants With Progression-free Survival (PFS) Events According to RECIST v1.1 in Dose Expansion Phase [24]
    End point description
    The PFS is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. PD: at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. The number of participants with PFS events is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [24] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Participants with event
        number (not applicable)
    43
    32
    51
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.719
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.468
         upper limit
    		 1.105
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Dose-expansion, Gem + nab-pacli v Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.726
         upper limit
    		 1.837

    Secondary: Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase

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    End point title
    		 Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase [25]
    End point description
    Progression-free survival (PFS) is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. The PD is defined as at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [25] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Months
        median (confidence interval 95%)
    6.7 (5.5 to 9.0)
    5.6 (3.5 to 7.5)
    7.5 (5.5 to 10.9)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase

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    End point title
    		 Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase [26]
    End point description
    DoR: Time from first documentation of OR until first documentation of PD/death due to any cause, whichever occurred first. OR: Confirmed CR/PR based on RECIST v1.1. CR: Disappearance of all TLs and NTLs, any pathological TLN and NTLN must had reduction in short axis <10 mm and no new lesions. PR: At least 30% decrease in SoD of TLs and no new lesions. Confirmation of CR and PR is required by repeat,consecutive assessment no less than 4 weeks from first documentation date. PD: At least 20% increase in SoD of TLs and absolute increase of at least 5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion/s. DoR is assessed using Kaplan-Meier method. ITT population included all participants who received any study drugs and analyzed according to randomized treatment assignment. DoR is assessed for only those participants who had OR. The arbitrary number 99.99 signified upper limit confidence interval (CI) could not be derived due to insufficient events being observed.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [26] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    18
    8
    23
    Units: Months
        median (confidence interval 95%)
    7.2 (4.9 to 99.99)
    12.9 (2.2 to 99.99)
    9.5 (5.7 to 12.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase

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    End point title
    		 Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase [27]
    End point description
    DC: defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis <10 mm, and no new lesions. The PR is at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from first documentation date. The SD is neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for PD, and no new lesions. The PD is at least 20% increase in SoD of TLs and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. The ITT population included all participants who were randomized and received any study drugs and analyzed according to randomized treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    Notes
    [27] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    62
    38
    70
    Units: Percentage of Participants
        number (confidence interval 95%)
    66.1 (53.0 to 77.7)
    73.7 (56.9 to 86.6)
    75.7 (64.0 to 85.2)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

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    End point title
    		 Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    OR: Best overall response of confirmed CR/PR based on RECIST v1.1. CR: Disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must had reduction in short axis <10 mm, and no new lesions. PR: At least 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than weeks from first documentation date. The OR is assessed by cluster of differentiation 73 (CD73) expression level either low or high at baseline. CD73 low: No CD73 expression in tumor cells or <50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Percentage of Participants
        number (confidence interval 95%)
    23.9 (12.6 to 38.8)
    22.2 (8.6 to 42.3)
    31.4 (19.1 to 45.9)
    43.8 (19.8 to 70.1)
    18.2 (2.3 to 51.8)
    36.8 (16.3 to 61.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.2
         upper limit
    		 21.9
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -25.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.3
         upper limit
    		 13.9
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    -6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.1
         upper limit
    		 26.6
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Rate difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.6
         upper limit
    		 27

    Secondary: Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase

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    End point title
    		 Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. The number of participants with overall survival events (deaths) is reported. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Participants with events
        number (not applicable)
    37
    22
    39
    10
    10
    14
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.676
         upper limit
    		 1.985
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.472
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.638
         upper limit
    		 3.576
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.549
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.622
         upper limit
    		 3.917
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.605
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.377
         upper limit
    		 0.968

    Secondary: Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase

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    End point title
    		 Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, "number of subjects analyzed" (N) signified those participants who had high or low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Months
        median (confidence interval 95%)
    9.9 (6.8 to 12.2)
    7.9 (4.2 to 9.7)
    12.1 (8.6 to 15.0)
    22.2 (10.2 to 33.6)
    16.0 (5.7 to 22.6)
    16.1 (10.3 to 21.0)
    No statistical analyses for this end point

    Secondary: Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

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    End point title
    		 Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    PFS: Time from randomization until first documentation of PD/death due to any cause, whichever occurred first, regardless of whether participant received subsequent anticancer treatment prior to progression. PD:>=20% increase in SoD of TLs and an absolute increase of >= 5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion. Participants who had no documented progression and were still alive at the time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. Number of participants with PFS events is reported. ITT population was analyzed for this endpoint. "Number of subjects analyzed" (N) signified those participants who had high/low levels of CD73.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Participants with event
        number (not applicable)
    35
    23
    39
    8
    9
    12
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.598
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.366
         upper limit
    		 0.973
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = High v Ole 3000 mg + Gem + nab-pacli: CD73 level = High
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.584
         upper limit
    		 1.693
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.374
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 3.707
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Hazard ratio for comparison between treatment groups obtained from Cox Proportional Hazards model stratified by CD73 level with ties handled by the Efron method.
    Comparison groups
    Gem + nab-pacli: CD73 level = Low v Ole 3000 mg + Gem + nab-pacli: CD73 level = Low
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.933
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.716
         upper limit
    		 5.437

    Secondary: Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

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    End point title
    		 Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
    End point description
    PFS:Time from randomization until first documentation of PD/death due to any cause, whichever occurred first, regardless of subsequent anticancer treatment prior to progression. PD:>=20% increase in SoD of TLs and absolute increase of >=5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion. Participants who had no documented progression and were still alive at time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. ITT population was analyzed for this endpoint. "Number of subjects analyzed"(N) signified those participants who had high/low levels of CD73. Arbitrary number 99.99 signified upper limit CI could not be derived due to insufficient events.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
    End point values
    		 Gem + nab-pacli: CD73 level = High Ole 3000 mg + Gem + nab-pacli: CD73 level = High Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = High Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Gem + nab-pacli: CD73 level = Low Ole 3000 mg + Durva + Gem + nab-pacli: CD73 level = Low
    Number of subjects analysed
    46
    27
    51
    16
    11
    19
    Units: Months
        median (confidence interval 95%)
    5.6 (3.7 to 7.4)
    5.2 (1.9 to 6.3)
    5.5 (4.4 to 9.3)
    10.5 (6.9 to 99.99)
    7.6 (3.3 to 11.2)
    10.9 (5.7 to 13.2)
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab

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    End point title
    		 Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab [28]
    End point description
    Number of participants with positive ADA to oleclumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. The ADA evaluable oleclumab population included all participants who received oleclumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
    End point type
    Secondary
    End point timeframe
    Day 1 through 172.1 weeks (Pre-dose on Cycle [C] 1 Day [D] 1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of oleclumab)
    Notes
    [28] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    6
    7
    3
    7
    31
    63
    Units: Participants
        ADA positive at baseline
    0
    0
    0
    0
    0
    0
        ADA positive post-baseline
    1
    0
    0
    1
    1
    0
        Persistent Positive
    1
    0
    0
    1
    0
    0
        Transient Positive
    0
    0
    0
    0
    1
    0
        Treatment-boosted ADA
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive ADA to Durvalumab

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    End point title
    		 Number of Participants With Positive ADA to Durvalumab [29]
    End point description
    Number of participants with positive ADA to durvalumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. The ADA evaluable durvalumab population included all participants who received durvalumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
    End point type
    Secondary
    End point timeframe
    Day 1 through 128 weeks (Pre-dose on C1D1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of durvalumab)
    Notes
    [29] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    6
    7
    3
    7
    60
    Units: Participants
        ADA positive at baseline
    0
    0
    0
    0
    2
        ADA positive post-baseline
    1
    0
    0
    2
    0
        Persistent Positive
    1
    0
    0
    2
    0
        Transient Positive
    0
    0
    0
    0
    0
        Treatment-boosted ADA
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Oleclumab

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    End point title
    		 Serum Concentrations of Oleclumab [30]
    End point description
    Serum concentrations of oleclumab are reported. Pharmacokinetic (PK) evaluable oleclumab population included all participants who received at least one dose of oleclumab and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm. The arbitrary numbers 999.99 and 9999.9 signified that the geometric mean and geometric CV% could not be calculated as no participant was analysed at that time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten minutes (mins) (± 5 mins) post end of infusion (EOI), approximately 1 hour (+ 15 mins) after start of infusion on C1D1, C3D1, and C5D1; and pre-dose on C3D1 and C5D1
    Notes
    [30] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    3
    8
    38
    70
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,3,7,37,70)
    297.6 ( 25.70 )
    710.2 ( 21.42 )
    412.7 ( 11.12 )
    734.6 ( 41.01 )
    704.4 ( 30.28 )
    725.9 ( 34.69 )
        C3D1 (pre-dose) (n=3,5,3,4,27,57)
    128.6 ( 10.00 )
    211.5 ( 73.40 )
    134.3 ( 141.5 )
    368.9 ( 2.461 )
    164.8 ( 324.1 )
    226.8 ( 70.41 )
        C3D1 (EOI) (n=2,5,3,4,25,57)
    0.99999 ( 99999 )
    870.3 ( 21.86 )
    571.1 ( 15.75 )
    1181 ( 24.97 )
    893.0 ( 30.66 )
    894.4 ( 39.22 )
        C5D1 (pre-dose) (n=1,3,0,4,20,45)
    0.99999 ( 99999 )
    73.19 ( 130.2 )
    999.99 ( 9999.9 )
    235.7 ( 27.68 )
    85.99 ( 192.0 )
    116.4 ( 54.0 )
        C5D1 (EOI) (n=1,3,0,4,20,45)
    0.99999 ( 99999 )
    948.3 ( 44.90 )
    999.99 ( 9999.9 )
    1057 ( 14.88 )
    852.8 ( 24.77 )
    753.2 ( 41.32 )
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Durvalumab

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    End point title
    		 Serum Concentrations of Durvalumab [31]
    End point description
    Serum concentrations of durvalumab are reported. The PK evaluable durvalumab population included all participants who received at least one dose of durvalumab and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm. The arbitrary numbers 999.99 and 9999.9 signified that the geometric mean and geometric CV% could not be calculated as no participant was analysed at that time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 1 hour (+ 15 mins) after start of infusion on C1D1 and C5D1; and pre-dose on C2D1 and C5D1
    Notes
    [31] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    3
    8
    70
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,3,8,70)
    292.5 ( 11.72 )
    374.5 ( 27.50 )
    309.0 ( 11.58 )
    380.7 ( 56.89 )
    345.8 ( 324.2 )
        C2D1 (pre-dose) (n=5,6,3,7,61)
    35.97 ( 51.44 )
    14.39 ( 5129 )
    50.52 ( 57.30 )
    59.97 ( 176.7 )
    86.20 ( 97.95 )
        C5D1 (pre-dose) (n=1,3,0,4,45)
    0.99999 ( 99999 )
    74.52 ( 28.32 )
    999.99 ( 9999.9 )
    175.9 ( 43.50 )
    137.9 ( 48.85 )
        C5D1 (EOI) (n=1,3,0,4,44)
    0.99999 ( 99999 )
    522.1 ( 46.72 )
    999.99 ( 9999.9 )
    664.5 ( 28.14 )
    597.9 ( 23.40 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Gemcitabine and Metabolite 2’,2’-Difluorodeoxyuridine (dFdU)

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    End point title
    		 Plasma Concentrations of Gemcitabine and Metabolite 2’,2’-Difluorodeoxyuridine (dFdU) [32]
    End point description
    Plasma concentrations of gemcitabine and metabolite dFdU are reported. The PK evaluable gemcitabine population included all participants who received at least one dose of gemcitabine and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
    Notes
    [32] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    57
    38
    70
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Gemcitabine C1D1 (EOI) (n=7,7,54,36,65)
    3194 ( 64.74 )
    4659 ( 67.41 )
    3301 ( 192.0 )
    3315 ( 135.4 )
    4086 ( 148.9 )
        Gemcitabine C4D1 (pre-dose) (n=2,4,33,25,50)
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
        Gemcitabine C4D1 (EOI) (n=2,4,28,25,49)
    0.99999 ( 99999 )
    3530 ( 48.11 )
    1748 ( 236.5 )
    1431 ( 446.3 )
    2998 ( 151.3 )
        dFdU C1D1 (EOI) (n=7,7,54,36,65)
    33700 ( 14.70 )
    32160 ( 17.67 )
    29510 ( 113.4 )
    32350 ( 17.10 )
    26300 ( 163.9 )
        dFdU C4D1 (pre-dose) (n=2,4,33,25,50)
    0.99999 ( 99999 )
    434.6 ( 344.7 )
    245.1 ( 361.5 )
    149.9 ( 147.0 )
    177.5 ( 170.0 )
        dFdU C4D1 (EOI) (n=2,4,28,25,49)
    0.99999 ( 99999 )
    34550 ( 35.37 )
    23900 ( 189.1 )
    21970 ( 130.3 )
    27260 ( 43.07 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Nab-paclitaxel

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    End point title
    		 Plasma Concentrations of Nab-paclitaxel [33]
    End point description
    Plasma concentrations of nab-paclitaxel are reported. The PK evaluable nab-paclitaxel population included all participants who received at least one dose of nab-paclitaxel and who had at least one reportable PK concentration. Here, n (number analyzed) denotes those participants who were analyzed for the specified time points. The arbitrary numbers 0.99999 and 99999 signified that the geometric mean and geometric CV% were not calculated at the time point. This was because, as per sponsor convention, three observations > Lower Limit of Quantification were required as a minimum for a plasma concentration to be summarised. Otherwise, the statistics were not calculated at the time point for the specified arm.
    End point type
    Secondary
    End point timeframe
    Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
    Notes
    [33] - 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 those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Number of subjects analysed
    7
    7
    60
    38
    70
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1 (EOI) (n=7,7,58,35,69)
    1711 ( 80.37 )
    2685 ( 63.55 )
    2381 ( 105.2 )
    2711 ( 81.67 )
    2611 ( 142.0 )
        C4D1 (pre-dose) (n=2,4,35,24,47)
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
    0.99999 ( 99999 )
        C4D1 (EOI) (n=2,4,31,24,48)
    0.99999 ( 99999 )
    1474 ( 96.12 )
    1825 ( 178.1 )
    1445 ( 145.8 )
    1747 ( 99.26 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through 172.1 weeks (maximum observed duration)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 1500 mg + Durva + mFOLFOX
    Reporting group description
    		 -

    Reporting group title
    Dose-escalation, Ole 3000 mg + Durva + mFOLFOX
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Ole 3000 mg + Gem + nab-pacli
    Reporting group description
    		 -

    Reporting group title
    Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Reporting group description
    		 -

    Serious adverse events
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 7 (57.14%)
    6 / 7 (85.71%)
    0 / 3 (0.00%)
    4 / 8 (50.00%)
    34 / 62 (54.84%)
    24 / 38 (63.16%)
    37 / 70 (52.86%)
         number of deaths (all causes)
    7
    7
    3
    8
    47
    32
    53
         number of deaths resulting from adverse events
    1
    0
    0
    0
    3
    1
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Shock
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Localised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    3 / 38 (7.89%)
    8 / 70 (11.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    3 / 6
    3 / 3
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    4 / 70 (5.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemolytic uraemic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    4 / 62 (6.45%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    2 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    5 / 62 (8.06%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 1
    3 / 5
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder rupture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bullous impetigo
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Hepatic infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    4 / 62 (6.45%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Dose-escalation, Ole 1500 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 3000 mg + Durva + Gem + nab-pacli Dose-escalation, Ole 1500 mg + Durva + mFOLFOX Dose-escalation, Ole 3000 mg + Durva + mFOLFOX Dose-expansion, Gem + nab-pacli Dose-expansion, Ole 3000 mg + Gem + nab-pacli Dose-expansion, Ole 3000 mg + Durva + Gem + nab-pacli
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    60 / 62 (96.77%)
    36 / 38 (94.74%)
    70 / 70 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cancer fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cryoglobulinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Deep vein thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    0
    0
    5
    3
    1
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Flushing
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    3 / 38 (7.89%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    3
    Orthostatic hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 62 (3.23%)
    3 / 38 (7.89%)
    10 / 70 (14.29%)
         occurrences all number
    0
    0
    0
    1
    2
    7
    15
    Hypotension
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    4 / 38 (10.53%)
    4 / 70 (5.71%)
         occurrences all number
    2
    1
    0
    1
    3
    4
    4
    Haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Phlebitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Superficial vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Asthenia
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    8 / 62 (12.90%)
    4 / 38 (10.53%)
    7 / 70 (10.00%)
         occurrences all number
    2
    2
    0
    0
    9
    9
    10
    Catheter site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    6 / 38 (15.79%)
    9 / 70 (12.86%)
         occurrences all number
    0
    0
    0
    0
    3
    11
    10
    Early satiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    6 / 7 (85.71%)
    7 / 7 (100.00%)
    2 / 3 (66.67%)
    6 / 8 (75.00%)
    30 / 62 (48.39%)
    25 / 38 (65.79%)
    41 / 70 (58.57%)
         occurrences all number
    6
    9
    2
    7
    33
    60
    54
    Feeling abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gait disturbance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Generalised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Hypothermia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Localised oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    Influenza like illness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    1 / 38 (2.63%)
    7 / 70 (10.00%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    10
    Infusion site extravasation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    2 / 38 (5.26%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Injection site reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Illness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    13 / 62 (20.97%)
    12 / 38 (31.58%)
    28 / 70 (40.00%)
         occurrences all number
    4
    4
    0
    2
    15
    21
    41
    Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    2
    0
    0
    1
    1
    2
    1
    Peripheral swelling
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    2 / 38 (5.26%)
    1 / 70 (1.43%)
         occurrences all number
    2
    0
    0
    0
    1
    2
    1
    Pyrexia
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    10 / 62 (16.13%)
    10 / 38 (26.32%)
    18 / 70 (25.71%)
         occurrences all number
    4
    2
    0
    1
    14
    16
    26
    Temperature intolerance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    3 / 38 (7.89%)
    3 / 70 (4.29%)
         occurrences all number
    0
    0
    1
    1
    3
    3
    3
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    1
    0
    0
    2
    3
    1
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    Unevaluable event
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Immunisation reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Infusion related hypersensitivity reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    2 / 62 (3.23%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Pelvic discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Prostatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    1 / 38 (2.63%)
    2 / 70 (2.86%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    2
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    5 / 62 (8.06%)
    4 / 38 (10.53%)
    11 / 70 (15.71%)
         occurrences all number
    1
    2
    0
    0
    6
    5
    13
    Dysphonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 62 (0.00%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    6 / 62 (9.68%)
    6 / 38 (15.79%)
    7 / 70 (10.00%)
         occurrences all number
    1
    0
    0
    0
    7
    6
    7
    Bronchiectasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 62 (1.61%)
    0 / 38 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 62 (4.84%)
    2 / 38 (5.26%)
    5 / 70 (7.14%)
         occurrences all number
    2
    0
    0
    0
    3
    2
    6
    Hiccups
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 62 (4.84%)
    1 / 38 (2.63%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    1
    3
    2
    1
    Hypoxia