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    Clinical Trial Results:
    A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) In Combination with CHOP or CHP-Polatuzumab Vedotin in Patients with B Cell Non-Hodgkin Lymphoma

    Summary
    EudraCT number
    		 2018-001039-29
    Trial protocol
    		 FR   AT   ES  
    Global end of trial date
    12 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Oct 2024
    First version publication date
    27 Oct 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GO40515
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03677141
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, 4058
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    23 Jan 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to assess safety and tolerability of mosunetuzumab in combination with CHOP and in combination with CHP-pola (Phase Ib), and to compare M-CHP-pola with rituximab in combination with CHP-pola in participants with previously untreated DLBCL (Phase II).
    Protection of trial subjects
    Participants were required to sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Oct 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 14
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 13
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    United States: 63
    Worldwide total number of subjects
    117
    EEA total number of subjects
    41
    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)
    51
    From 65 to 84 years
    65
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Phase Ib: Participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Phase II: Participants with previously untreated diffuse large B-cell lymphoma (DLBCL).

    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
    		 Group A1: Phase Ib Mosunetuzumab + CHOP
    Arm description
    		 Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mosunetuzumab
    Investigational medicinal product code
    Other name
    RO7030816; BTCT4465A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received intravenous (IV) mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6 (cycle length = 21 days). Participants with stable disease (SD) or partial response (PR) at the end of 6 cycles were eligible to receive mosunetuzumab monotherapy for up to 11 additional cycles on Day 1 of each cycle.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV vincristine on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    RO0452294
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV rituximab on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Arm title
    		 Group A2: Phase Ib Mosunetuzumab + CHOP
    Arm description
    		 Participants with relapsed/refractory (R/R) B-cell NHL received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5. Treatment was given for 6 cycles (cycle length = 21 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mosunetuzumab
    Investigational medicinal product code
    Other name
    RO7030816; BTCT4465A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received intravenous (IV) mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6 (cycle length = 21 days). Participants with stable disease (SD) or partial response (PR) at the end of 6 cycles were eligible to receive mosunetuzumab monotherapy for up to 11 additional cycles on Day 1 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV vincristine on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Arm title
    		 Group B: Phase Ib Mosunetuzumab + M-CHP-Pola
    Arm description
    		 Participants with R/R NHL received 6 cycles of mosunetuzumab (M) + cyclophosphamide, doxorubicin, prednisone (CHP), and polatuzumab vedotin (Pola) (cycle length = 21 days). Participants received M on C1D2, C1D8, and C1D15, C2D2, and on D1 of subsequent cycles if well tolerated. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mosunetuzumab
    Investigational medicinal product code
    Other name
    RO7030816; BTCT4465A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV mosunetuzumab on C1D2,C1D8, C1D15, C2D2, and on D1 of subsequent cycles if well tolerated (cycle length = 21 days). Participants with SD or PR at the end of 6 cycles were eligible to receive mosunetuzumab monotherapy for up to 11 additional cycles on on Day 1 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Polatuzumab vedotin
    Investigational medicinal product code
    Other name
    RO5541077
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV polatuzumab vedotin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Arm title
    		 Group C: Phase II Mosunetuzumab + CHOP
    Arm description
    		 Participants with previously untreated diffuse large B-cell lymphoma (DLBCL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mosunetuzumab
    Investigational medicinal product code
    Other name
    RO7030816; BTCT4465A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received intravenous (IV) mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6 (cycle length = 21 days). Participants with stable disease (SD) or partial response (PR) at the end of 6 cycles were eligible to receive mosunetuzumab monotherapy for up to 11 additional cycles on Day 1 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV vincristine on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Arm title
    		 Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Arm description
    		 Participants received M-CHP-Pola for 6 cycles (cycle length = 21 days). Participants received M on C1D1, C1D8, and C1D15, then on D1 of subsequent cycles. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mosunetuzumab
    Investigational medicinal product code
    Other name
    RO7030816; BTCT4465A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV mosunetuzumab on Days 1, 8, and 15 of Cycle 1, then on Day 1 of subsequent cycles (cycle length = 21 days). Participants with SD or PR at the end of 6 cycles were eligible to receive mosunetuzumab monotherapy for up to 11 additional cycles on on Day 1 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Polatuzumab vedotin
    Investigational medicinal product code
    Other name
    RO5541077
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV polatuzumab vedotin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Arm title
    		 Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Arm description
    		 Participants received R-CHP-Pola for 6 cycles (cycle length = 21 days). R-CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV cyclophosphamide on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Polatuzumab vedotin
    Investigational medicinal product code
    Other name
    RO5541077
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV polatuzumab vedotin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV doxorubicin on Day 1 of each cycle for 6 cycles (cycle length = 21 days).

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received prednisone once daily by mouth (PO) on Days 1-5 of each cycle for 6 cycles (cycle length = 21 days).

    Number of subjects in period 1
    		Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Started
    3
    4
    8
    40
    40
    22
    Completed
    1
    3
    1
    28
    31
    19
    Not completed
    2
    1
    7
    12
    9
    3
         Adverse event, serious fatal
    2
    1
    6
    9
    5
    3
         Consent withdrawn by subject
    -
    -
    1
    1
    1
    -
         Screen failure or enrolled in error
    -
    -
    -
    -
    2
    -
         Physician decision
    -
    -
    -
    -
    1
    -
         Lost to follow-up
    -
    -
    -
    2
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A1: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group A2: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell NHL received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5. Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group B: Phase Ib Mosunetuzumab + M-CHP-Pola
    Reporting group description
    		 Participants with R/R NHL received 6 cycles of mosunetuzumab (M) + cyclophosphamide, doxorubicin, prednisone (CHP), and polatuzumab vedotin (Pola) (cycle length = 21 days). Participants received M on C1D2, C1D8, and C1D15, C2D2, and on D1 of subsequent cycles if well tolerated. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Group C: Phase II Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with previously untreated diffuse large B-cell lymphoma (DLBCL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received M-CHP-Pola for 6 cycles (cycle length = 21 days). Participants received M on C1D1, C1D8, and C1D15, then on D1 of subsequent cycles. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received R-CHP-Pola for 6 cycles (cycle length = 21 days). R-CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group values
    		 Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized) Total
    Number of subjects
    		 3 4 8 40 40 22 117
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 1 0 5 19 14 12 51
        From 65-84 years
    		 1 4 3 21 26 10 65
        85 years and over
    		 1 0 0 0 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 72.0 ( 13.0 ) 71.3 ( 3.4 ) 60.1 ( 18.0 ) 63.4 ( 11.0 ) 65.0 ( 10.0 ) 57.7 ( 14.3 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 0 1 3 18 14 8 44
        Male
    		 3 3 5 22 26 14 73
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 1 0 1
        Asian
    		 0 0 0 10 5 0 15
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 1 1
        White
    		 3 4 8 28 30 20 93
        More than one race
    		 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 2 4 1 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 1 3 3 2 3 12
        Not Hispanic or Latino
    		 3 3 5 36 35 18 100
        Unknown or Not Reported
    		 0 0 0 1 3 1 5

    End points

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    End points reporting groups
    Reporting group title
    Group A1: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group A2: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell NHL received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5. Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group B: Phase Ib Mosunetuzumab + M-CHP-Pola
    Reporting group description
    		 Participants with R/R NHL received 6 cycles of mosunetuzumab (M) + cyclophosphamide, doxorubicin, prednisone (CHP), and polatuzumab vedotin (Pola) (cycle length = 21 days). Participants received M on C1D2, C1D8, and C1D15, C2D2, and on D1 of subsequent cycles if well tolerated. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Group C: Phase II Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with previously untreated diffuse large B-cell lymphoma (DLBCL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received M-CHP-Pola for 6 cycles (cycle length = 21 days). Participants received M on C1D1, C1D8, and C1D15, then on D1 of subsequent cycles. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received R-CHP-Pola for 6 cycles (cycle length = 21 days). R-CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Primary: Complete response (CR) rate at the time of primary response assessment (PRA) based on positron emission tomography - computed tomography (PET-CT) as determined by independent review committee (IRC)

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    End point title
    		 Complete response (CR) rate at the time of primary response assessment (PRA) based on positron emission tomography - computed tomography (PET-CT) as determined by independent review committee (IRC) [1]
    End point description
    The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria. The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory. The primary efficacy analysis compared Arm 1 vs Arm 2, with participants grouped according to the treatment arm assigned at randomization. Group C was included in secondary efficacy analysis, and efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Primary
    End point timeframe
    6-8 weeks after either C6D1 or last dose of study treatment
    Notes
    [1] - 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: Efficacy analyses for Arms A1, A2, and B were exploratory. The primary efficacy analysis compared Arm 1 vs Arm 2, with participants grouped according to the treatment arm assigned at randomization. Group C was included in secondary efficacy analysis.
    End point values
    		 Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    22
    Units: Percentage of participants
        number (confidence interval 95%)
    72.5 (56.11 to 85.40)
    77.3 (54.63 to 92.18)
    Statistical analysis title
    		 CR rate at PRA by IRC based on PET-CT
    Comparison groups
    Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) v Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in rates
    Point estimate
    -4.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.61
         upper limit
    		 21.07

    Secondary: CR rate at PRA based on CT only as determined by the investigator (Phase II)

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    End point title
    		 CR rate at PRA based on CT only as determined by the investigator (Phase II) [2]
    End point description
    The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after either C6D1 or last dose of study treatment
    Notes
    [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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    40
    22
    Units: Percentage of participants
        number (confidence interval 95%)
    50.0 (33.80 to 66.20)
    47.5 (31.51 to 63.87)
    31.8 (13.86 to 54.87)
    No statistical analyses for this end point

    Secondary: Overall response rate (ORR) at PRA based on PET-CT as determined by the investigator (Phase II)

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    End point title
    		 Overall response rate (ORR) at PRA based on PET-CT as determined by the investigator (Phase II) [3]
    End point description
    ORR is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator. The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after either C6D1 or last dose of study treatment
    Notes
    [3] - 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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    40
    22
    Units: Percentage of participants
    number (confidence interval 95%)
        ORR
    87.5 (73.20 to 95.81)
    80.0 (64.35 to 90.95)
    77.3 (54.63 to 92.18)
    No statistical analyses for this end point

    Secondary: ORR at PRA based on CT only as determined by the investigator (Phase II)

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    End point title
    		 ORR at PRA based on CT only as determined by the investigator (Phase II) [4]
    End point description
    ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator. The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after either C6D1 or last dose of study treatment
    Notes
    [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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    40
    22
    Units: Percentage of participants
        number (confidence interval 95%)
    85.0 (70.16 to 94.29)
    72.5 (56.11 to 85.40)
    81.8 (59.72 to 94.81)
    No statistical analyses for this end point

    Secondary: Best ORR based on PET-CT and/or CT scan as determined by the investigator (Phase II)

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    End point title
    		 Best ORR based on PET-CT and/or CT scan as determined by the investigator (Phase II) [5]
    End point description
    Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator. The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    Up to approximately 50 months
    Notes
    [5] - 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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    36
    22
    Units: Percentage of responders
    number (confidence interval 95%)
        Best ORR
    95.0 (83.08 to 99.39)
    85.0 (70.16 to 94.29)
    95.5 (77.16 to 99.88)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) as determined by the investigator (Phase II)

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    End point title
    		 Progression-free survival (PFS) as determined by the investigator (Phase II) [6]
    End point description
    PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. Efficacy analyses for Arms A1, A2, and B were exploratory. The number of participants analyzed reflects the number of participants with the event. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day). The median values for each arm could not be determined due to an insufficient number of participants with the event. The values in those fields are placeholder values.
    End point type
    Secondary
    End point timeframe
    Up to approximately 50 months
    Notes
    [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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    40
    22
    Units: Months
        median (full range (min-max))
    0 (0 to 31)
    0 (0 to 30)
    3 (3 to 30)
    No statistical analyses for this end point

    Secondary: Duration of response (DOR) as determined by the investigator (Phase II)

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    End point title
    		 Duration of response (DOR) as determined by the investigator (Phase II) [7]
    End point description
    DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The number of participants analyzed was the number of participants with a PR or CR in each arm. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment). The median values for each arm could not be determined due to an insufficient number of participants with the event. The values in those fields are placeholder values.
    End point type
    Secondary
    End point timeframe
    Up to approximately 50 months
    Notes
    [7] - 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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    38 [8]
    34 [9]
    21 [10]
    Units: Months
        median (full range (min-max))
    0 (0 to 28)
    0 (0 to 28)
    1 (1 to 27)
    Notes
    [8] - The median could not be determined due to an insufficient number of participants with the event.
    [9] - The median could not be determined due to an insufficient number of participants with the event.
    [10] - The median could not be determined due to an insufficient number of participants with the event.
    No statistical analyses for this end point

    Secondary: PFS at 1 year as determined by the investigator (Phase II)

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    End point title
    		 PFS at 1 year as determined by the investigator (Phase II) [11]
    End point description
    PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    1 year
    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: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    40
    22
    Units: Percentage of participants
        number (confidence interval 95%)
    77.47 (63.65 to 91.29)
    70.83 (55.59 to 86.07)
    81.82 (65.70 to 97.94)
    No statistical analyses for this end point

    Secondary: Event-free survival (EFS) as determined by the investigator (Phase II)

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    End point title
    		 Event-free survival (EFS) as determined by the investigator (Phase II) [12]
    End point description
    EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. Efficacy analyses for Arms A1, A2, and B were exploratory. The number of participants analyzed reflects the number of participants with the event. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment). The median values for each arm could not be determined due to an insufficient number of participants with the event. The values in those fields are placeholder values.
    End point type
    Secondary
    End point timeframe
    Up to 50 months
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point values
    		 Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    12
    11
    5
    Units: Months
        median (full range (min-max))
    2 (2 to 31)
    0 (0 to 30)
    3 (3 to 30)
    No statistical analyses for this end point

    Secondary: Time to deterioration in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) subscale

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    End point title
    		 Time to deterioration in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) subscale [13]
    End point description
    The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was specific to the arms reported.
    End point values
    		 Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    22
    Units: Months
        median (confidence interval 95%)
    9999 (2.3 to 9999)
    6.5 (2.1 to 9999)
    No statistical analyses for this end point

    Secondary: Time to deterioration in physical functioning and fatigue as measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)

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    End point title
    		 Time to deterioration in physical functioning and fatigue as measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) [14]
    End point description
    The intent-to-treat (ITT) population consisted of all participants. Efficacy analyses for Arms A1, A2, and B were exploratory.
    End point type
    Secondary
    End point timeframe
    C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was specific to the arms reported.
    End point values
    		 Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    40
    22
    Units: Months
        median (confidence interval 95%)
    2.3 (1.2 to 5.4)
    2.3 (0.8 to 9999)
    No statistical analyses for this end point

    Secondary: Polatuzumab Vedotin Serum Concentrations

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    End point title
    		 Polatuzumab Vedotin Serum Concentrations [15]
    End point description
    Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint.
    End point type
    Secondary
    End point timeframe
    C2D1, C6D1
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was specific to arms assigned to treatment with polatuzumab vedotin.
    End point values
    		 Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    8 [16]
    40 [17]
    22 [18]
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        C2D1 pre-dose
    0.993 ( 779.4 )
    1.99 ( 80.7 )
    1.73 ( 107.9 )
        C6D1 pre-dose
    2.76 ( 820.1 )
    8.13 ( 34.5 )
    5.8 ( 42 )
    Notes
    [16] - C2D1 n = 6 C6D1 n= 4
    [17] - C2D1 n = 33 C6D1 n = 27
    [18] - C2D1 n = 18 C6D1 n = 20
    No statistical analyses for this end point

    Secondary: Polatuzumab Vedotin antibody-conjugated monomethyl auristatin E (acMMAE) Serum Concentrations

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    End point title
    		 Polatuzumab Vedotin antibody-conjugated monomethyl auristatin E (acMMAE) Serum Concentrations [19]
    End point description
    Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint. 999 = No data were collected at that timepoint.
    End point type
    Secondary
    End point timeframe
    C1D1-C6D1
    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: This endpoint was specific to arms assigned to treatment with polatuzumab vedotin.
    End point values
    		 Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    8 [20]
    40 [21]
    22 [22]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1 post-dose
    620 ( 54.5 )
    668 ( 21.2 )
    584 ( 23.1 )
        C1D2 pre-dose
    219 ( 412.2 )
    999 ( 999 )
    999 ( 999 )
        C1D2 24hrs post-dose
    115 ( 658.3 )
    275 ( 28.2 )
    999 ( 999 )
        C1D8 pre-dose
    23 ( 1040.4 )
    42 ( 82 )
    999 ( 999 )
        C1D15 pre-dose
    8.22 ( 550.4 )
    13.2 ( 87.4 )
    999 ( 999 )
        C2D1 pre-dose
    4.87 ( 626 )
    6.81 ( 80.1 )
    7.09 ( 95.5 )
        C2D1 post-dose
    656 ( 21.1 )
    653 ( 18 )
    654 ( 21 )
        C3D1 pre-dose
    19.2 ( 58.7 )
    15.8 ( 39.5 )
    999 ( 999 )
        C3D1 post-dose
    144 ( 112947.3 )
    544 ( 90.7 )
    999 ( 999 )
        C4D1 pre-dose
    16.8 ( 79.6 )
    16.8 ( 50.3 )
    15.6 ( 41.4 )
        C4D1 post-dose
    783 ( 26.5 )
    614 ( 15.4 )
    696 ( 24.1 )
        C5D1 pre-dose
    7.14 ( 343.5 )
    19 ( 39.7 )
    999 ( 999 )
        C5D1 post-dose
    544 ( 37.6 )
    605 ( 21.6 )
    999 ( 999 )
        C6D1 pre-dose
    11.8 ( 476.6 )
    21.2 ( 34.7 )
    17.3 ( 40.8 )
    Notes
    [20] - n = 8,7,8,7,7,6,6,5,5,4,4,3,3,4 respectively
    [21] - n = 22,0,24,29,30,31,32,33,30,33,30,29,9,25 respectively
    [22] - n = 16,0,0,0,0,18,13,0,0,21,18,0,0,19 respectively
    No statistical analyses for this end point

    Secondary: Polatuzumab Vedotin Unconjugated mono-methyl auristatin E (MMAE) Serum Concentrations

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    End point title
    		 Polatuzumab Vedotin Unconjugated mono-methyl auristatin E (MMAE) Serum Concentrations [23]
    End point description
    Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive polatuzumab vedotin were not included in this endpoint. 999 = No data were collected at that timepoint. 9999 = If more than one-third of values were lower than reportable, only the median, maximum, and geometric mean are reported.
    End point type
    Secondary
    End point timeframe
    C1D1-C6D1
    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: This endpoint was specific to arms assigned to treatment with polatuzumab vedotin.
    End point values
    		 Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    8 [24]
    40 [25]
    22 [26]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1 post-dose
    0.535 ( 464.6 )
    0.55 ( 71.1 )
    0.432 ( 78.8 )
        C1D2 pre-dose
    1.94 ( 114.2 )
    999 ( 999 )
    999 ( 999 )
        C1D2 24hrs post-dose
    3.3 ( 97.8 )
    2.82 ( 51.9 )
    999 ( 999 )
        C1D8 pre-dose
    2.95 ( 80.9 )
    1.27 ( 93.6 )
    999 ( 999 )
        C1D15 pre-dose
    0.604 ( 113.3 )
    0.301 ( 104.1 )
    999 ( 999 )
        C2D1 pre-dose
    0.187 ( 47.3 )
    0.0773 ( 110.2 )
    0.0697 ( 87 )
        C2D1 post-dose
    0.238 ( 64 )
    0.137 ( 84 )
    0.116 ( 56.3 )
        C3D1 pre-dose
    0.168 ( 92 )
    0.146 ( 96.9 )
    999 ( 999 )
        C3D1 post-dose
    0.111 ( 173.9 )
    0.203 ( 92.7 )
    999 ( 999 )
        C4D1 pre-dose
    0.0491 ( 9999 )
    0.14 ( 93.8 )
    0.106 ( 88.9 )
        C4D1 post-dose
    0.0825 ( 188.3 )
    0.186 ( 66.1 )
    0.164 ( 43.6 )
        C5D1 pre-dose
    0.0741 ( 247 )
    0.137 ( 74.4 )
    999 ( 999 )
        C5D1 post-dose
    0.212 ( 54.2 )
    0.17 ( 38.1 )
    999 ( 999 )
        C6D1 pre-dose
    0.0967 ( 194.2 )
    0.142 ( 63.8 )
    0.0974 ( 82.4 )
    Notes
    [24] - n = 8,7,8,7,7,6,6,5,5,4,4,3,3,4 respectively
    [25] - n = 29,0,30,30,30,33,35,33,32,33,30,30,7,27
    [26] - n = 16,0,0,0,0,18,14,0,0,21,18,0,0,19 respectively
    No statistical analyses for this end point

    Secondary: Mosunetuzumab Serum Concentrations

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    End point title
    		 Mosunetuzumab Serum Concentrations [27]
    End point description
    Participants with at least one pharmacokinetic (PK) sample were included in analysis. Arms in which participants did not receive mosunetuzumab were not included in this endpoint. 9999 = 0 participants analyzed for this timepoint.
    End point type
    Secondary
    End point timeframe
    C1D1-C5D1
    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: This endpoint was specific to arms assigned to treatment with mosunetuzumab.
    End point values
    		 Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Number of subjects analysed
    3 [28]
    4 [29]
    8 [30]
    40 [31]
    40 [32]
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        C1D1 post-dose
    0.157 ( 22.1 )
    0.181 ( 26.7 )
    9999 ( 9999 )
    0.155 ( 34.1 )
    0.132 ( 73.2 )
        C1D1 2 hrs post-dose
    0.152 ( 27.8 )
    0.163 ( 25.8 )
    9999 ( 9999 )
    0.151 ( 28.1 )
    9999 ( 9999 )
        C1D2 24 hrs post-dose
    0.103 ( 23.3 )
    0.112 ( 8.1 )
    0.0947 ( 60.2 )
    0.096 ( 35.7 )
    0.0825 ( 46.1 )
        C1D8 pre-dose
    0.0331 ( 49 )
    0.0218 ( 153.2 )
    0.0334 ( 113.6 )
    0.0253 ( 62.2 )
    0.0263 ( 77 )
        C1D8 post-dose
    0.342 ( 18.8 )
    0.427 ( 36.2 )
    0.354 ( 36.9 )
    0.426 ( 30.3 )
    0.376 ( 38.8 )
        C1D8 2hrs post-dose
    0.32 ( 28.5 )
    0.409 ( 50.1 )
    0.349 ( 43.1 )
    0.388 ( 27.6 )
    9999 ( 9999 )
        C1D15 pre-dose
    0.0866 ( 47.9 )
    0.0884 ( 52.8 )
    0.0911 ( 57.7 )
    0.0953 ( 41.8 )
    0.102 ( 47.7 )
        C1D15 post-dose
    2.83 ( 22.6 )
    5.71 ( 38.6 )
    5.72 ( 44 )
    7.13 ( 27.7 )
    6.31 ( 34.8 )
        C1D15 2 hrs post-dose
    2.28 ( 7.5 )
    5.66 ( 38.7 )
    5.92 ( 18.5 )
    6.56 ( 28.4 )
    9999 ( 9999 )
        C2D1 pre-dose
    0.549 ( 24.3 )
    1.52 ( 49.4 )
    9999 ( 9999 )
    1.67 ( 32.1 )
    1.46 ( 62.8 )
        C2D1 post-dose
    2.86 ( 7.2 )
    6.75 ( 42.2 )
    9999 ( 9999 )
    8.31 ( 27.4 )
    7.69 ( 38.3 )
        C2D1 2 hrs post-dose
    2.38 ( 1.2 )
    7.33 ( 44.7 )
    7.65 ( 35.1 )
    8.28 ( 26.7 )
    9999 ( 9999 )
        C2D2 pre-dose
    9999 ( 9999 )
    9999 ( 9999 )
    1.37 ( 38.6 )
    9999 ( 9999 )
    9999 ( 9999 )
        C2D2 post-dose
    9999 ( 9999 )
    9999 ( 9999 )
    8.9 ( 34.1 )
    9999 ( 9999 )
    9999 ( 9999 )
        C3D1 pre-dose
    0.458 ( 36.3 )
    1.08 ( 53.3 )
    1.21 ( 45.1 )
    1.11 ( 30.2 )
    0.885 ( 43 )
        C3D1 post-dose
    3.37 ( 23.4 )
    7.19 ( 30.8 )
    6.66 ( 41.3 )
    7.3 ( 39.2 )
    6.76 ( 28.9 )
        C4D1 pre-dose
    0.502 ( 36.9 )
    1.09 ( 44.4 )
    0.782 ( 90 )
    1.03 ( 33.9 )
    0.932 ( 52 )
        C4D1 post-dose
    3.24 ( 31.3 )
    7.38 ( 26.3 )
    4.09 ( 83 )
    7.41 ( 44 )
    5.55 ( 80.3 )
        C5D1 pre-dose
    0.426 ( 51.7 )
    1.02 ( 62 )
    0.33 ( 176.6 )
    1.12 ( 31.6 )
    0.935 ( 106.1 )
        C1D2 2 hrs post-dose
    9999 ( 9999 )
    9999 ( 9999 )
    0.145 ( 80 )
    9999 ( 9999 )
    9999 ( 9999 )
    Notes
    [28] - C1D15 2hrs post-dose - C2D1 2hrs post-dose n = 2
    [29] - C1D8 n = n = 3
    [30] - n = 0, 0, 8, 7, 7, 7, 7, 7, 7, 0, 0, 6, 6, 5, 5, 5, 4, 4, 3, 7 respectively
    [31] - n = 37, 35, 36, 39, 39, 38, 39, 39, 38, 37, 35, 34, 0, 0, 33, 34, 32, 32, 30, 0 respectively
    [32] - n = 22, 0, 29, 35, 35, 0, 31, 31, 0, 33, 30, 0, 0, 0, 8, 26, 32, 28, 4, 0 respectively
    No statistical analyses for this end point

    Secondary: Baseline prevalence and incidence of treatment emergent anti-drug antibodies (ADA) to Mosunetuzumab

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    End point title
    		 Baseline prevalence and incidence of treatment emergent anti-drug antibodies (ADA) to Mosunetuzumab [33]
    End point description
    Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected). The immunogenicity analysis population included all participants with at least one ADA assessment. The number of participants analyzed are the values for baseline-evaluable participants and post-baseline evaluable participants.
    End point type
    Secondary
    End point timeframe
    Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
    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: This endpoint was specific to arms assigned to treatment with mosunetuzumab.
    End point values
    		 Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Number of subjects analysed
    3
    4
    8 [34]
    40 [35]
    38 [36]
    Units: Number of participants
        Positive sample at baseline
    0
    0
    0
    0
    0
        Not positive at baseline
    3
    4
    8
    38
    33
        Positive for treatment-emergent ADA
    0
    0
    0
    0
    0
        Positive for treatment-induced ADA
    0
    0
    0
    0
    0
        Positive for treatment-enhanced ADA
    0
    0
    0
    0
    0
        Negative for treatment-emergent ADA
    3
    4
    6
    39
    37
    Notes
    [34] - n = 8, 8, 6, 6, 6, 6 respectively
    [35] - n = 38, 38, 39, 39, 39, 39 respectively
    [36] - n = 33, 33, 37, 37, 37, 37 respectively
    No statistical analyses for this end point

    Secondary: Baseline prevalence and incidence of treatment emergent ADA to Polatuzumab Vedotin

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    End point title
    		 Baseline prevalence and incidence of treatment emergent ADA to Polatuzumab Vedotin [37]
    End point description
    Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected). The immunogenicity analysis population included all participants with at least one ADA assessment. The number of participants analyzed are the values for baseline-evaluable participants and post-baseline evaluable participants.
    End point type
    Secondary
    End point timeframe
    Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)
    Notes
    [37] - 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: This endpoint was specific to arms assigned to treatment with polatuzumab vedotin.
    End point values
    		 Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Number of subjects analysed
    8 [38]
    38 [39]
    22 [40]
    Units: Number of participants
        Positive sample at baseline
    0
    1
    2
        Not positive at baseline
    8
    32
    19
        Positive for treatment-emergent ADA
    0
    0
    1
        Positive for treatment-induced ADA
    0
    0
    1
        Positive for treatment-enhanced ADA
    0
    0
    0
        Negative for treatment-emergent ADA
    6
    37
    20
    Notes
    [38] - n = 8, 8, 6, 6, 6, 6 respectively
    [39] - n = 38, 38, 37, 37, 37, 37 respectively
    [40] - n = 21 for each row
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 30 months
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v26.1
    Reporting groups
    Reporting group title
    Group A1: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group A2: Phase Ib Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with relapsed/refractory (R/R) B-cell NHL received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5. Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Group B: Phase Ib Mosunetuzumab + M-CHP-Pola
    Reporting group description
    		 Participants with R/R NHL received 6 cycles of mosunetuzumab (M) + cyclophosphamide, doxorubicin, prednisone (CHP), and polatuzumab vedotin (Pola) (cycle length = 21 days). Participants received M on C1D2, C1D8, C1D15, C2D2, and on D1 of subsequent cycles if well tolerated. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Group C: Phase II Mosunetuzumab + CHOP
    Reporting group description
    		 Participants with previously untreated diffuse large B-cell lymphoma (DLBCL) received mosunetuzumab on Cycle 1 Day 1 (C1D1), C1D8, and C1D15, then on Day 1 of subsequent cycles. In addition, participants received cyclophosphamide, doxorubicin, and vincristine on D1, and prednisone on D1-D5 (CHOP). Treatment was given for 6 cycles (cycle length = 21 days).

    Reporting group title
    Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received M-CHP-Pola for 6 cycles (cycle length = 21 days). Participants received M on C1D1, C1D8, and C1D15, then on D1 of subsequent cycles. CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Reporting group title
    Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Reporting group description
    		 Participants received R-CHP-Pola for 6 cycles (cycle length = 21 days). R-CHP-pola was given on D1 of each cycle (D1-D5 for prednisone).

    Serious adverse events
    		 Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    6 / 8 (75.00%)
    20 / 40 (50.00%)
    24 / 38 (63.16%)
    3 / 22 (13.64%)
         number of deaths (all causes)
    2
    1
    6
    9
    5
    3
         number of deaths resulting from adverse events
    2
    0
    4
    2
    3
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Malignant neoplasm progression
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Central nervous system lymphoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic rupture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypotension
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Death
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 2
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Peripheral swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    5 / 38 (13.16%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Troponin I increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Concussion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Anastomotic ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Anastomotic leak
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Angina unstable
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac tamponade
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Encephalopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune effector cell-associated neurotoxicity syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Lethargy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Syncope
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 1
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    6 / 40 (15.00%)
    5 / 38 (13.16%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    7 / 7
    5 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    3 / 38 (7.89%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    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
    Oesophageal fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Congestive hepatopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Urinary tract obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Cellulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Fungal oesophagitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Herpes zoster
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Influenza
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    3 / 38 (7.89%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Sepsis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    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
    Soft tissue infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Vascular device infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Failure to thrive
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group A1: Phase Ib Mosunetuzumab + CHOP Group A2: Phase Ib Mosunetuzumab + CHOP Group B: Phase Ib Mosunetuzumab + M-CHP-Pola Group C: Phase II Mosunetuzumab + CHOP Arm 1: Phase II Mosunetuzumab + CHP-Pola (randomized) Arm 2: Phase II Rituximab + CHP-Pola (randomized)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    8 / 8 (100.00%)
    40 / 40 (100.00%)
    38 / 38 (100.00%)
    22 / 22 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour flare
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    5
    1
    Hypotension
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    9 / 40 (22.50%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    1
    13
    2
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Superficial vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Pallor
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    5 / 40 (12.50%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    2
    0
    5
    2
    1
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    1
    1
    0
    0
    2
    Chest discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    3 / 38 (7.89%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    5 / 8 (62.50%)
    19 / 40 (47.50%)
    12 / 38 (31.58%)
    10 / 22 (45.45%)
         occurrences all number
    1
    2
    5
    23
    13
    13
    Generalised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    2
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    3 / 8 (37.50%)
    8 / 40 (20.00%)
    4 / 38 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    6
    13
    4
    0
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    8 / 40 (20.00%)
    5 / 38 (13.16%)
    0 / 22 (0.00%)
         occurrences all number
    3
    2
    3
    9
    7
    0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    24 / 40 (60.00%)
    22 / 38 (57.89%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    30
    27
    0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    7 / 40 (17.50%)
    4 / 38 (10.53%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    1
    7
    4
    3
    Cough
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    7 / 40 (17.50%)
    0 / 38 (0.00%)
    3 / 22 (13.64%)
         occurrences all number
    1
    2
    0
    9
    0
    3
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    1
    3
    0
    3
    Hiccups
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    3
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    2
    2
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    3
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    2 / 22 (9.09%)
         occurrences all number
    0
    1
    1
    1
    3
    2
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Confusional state
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hallucination
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    6 / 40 (15.00%)
    2 / 38 (5.26%)
    6 / 22 (27.27%)
         occurrences all number
    0
    0
    3
    6
    2
    6
    Restlessness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    2
    1
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    2
    1
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    6 / 40 (15.00%)
    10 / 38 (26.32%)
    4 / 22 (18.18%)
         occurrences all number
    0
    0
    0
    8
    10
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    5 / 40 (12.50%)
    6 / 38 (15.79%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    7
    6
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    1 / 38 (2.63%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    4
    1
    3
    Liver function test increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    2 / 22 (9.09%)
         occurrences all number
    0
    1
    1
    3
    2
    6
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    3
    1
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    1 / 38 (2.63%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    19
    3
    8
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    8 / 40 (20.00%)
    11 / 38 (28.95%)
    5 / 22 (22.73%)
         occurrences all number
    0
    2
    0
    13
    18
    7
    Platelet count decreased
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    5 / 40 (12.50%)
    4 / 38 (10.53%)
    3 / 22 (13.64%)
         occurrences all number
    4
    11
    1
    12
    8
    4
    Serum ferritin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    4 / 38 (10.53%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    1
    4
    4
    1
    White blood cell count decreased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 40 (7.50%)
    6 / 38 (15.79%)
    3 / 22 (13.64%)
         occurrences all number
    1
    0
    0
    10
    12
    7
    Injury, poisoning and procedural complications
    Vascular access site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Vascular access site haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vascular access complication
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Skin laceration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    2 / 40 (5.00%)
    9 / 38 (23.68%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    3
    2
    10
    3
    Febrile nonhaemolytic transfusion reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Fall
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    5
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Atrial flutter
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    5 / 40 (12.50%)
    3 / 38 (7.89%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    4
    6
    3
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    9 / 40 (22.50%)
    6 / 38 (15.79%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    9
    6
    0
    Ageusia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    7 / 40 (17.50%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    7
    2
    0
    Encephalopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Facial paralysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
    9 / 40 (22.50%)
    2 / 38 (5.26%)
    7 / 22 (31.82%)
         occurrences all number
    0
    2
    3
    14
    2
    8
    Horner's syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    5 / 38 (13.16%)
    4 / 22 (18.18%)
         occurrences all number
    0
    0
    0
    3
    6
    4
    Lacunar infarction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Memory impairment
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    13 / 40 (32.50%)
    3 / 38 (7.89%)
    4 / 22 (18.18%)
         occurrences all number
    2
    0
    0
    13
    3
    5
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    3
    2
    2
    Hypoaesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    Taste disorder
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    2
    1
    0
    Tremor
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    0
    2
    1
    1
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    3 / 38 (7.89%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    0
    1
    7
    2
    Leukocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    2
    1
    1
    Anaemia
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    17 / 40 (42.50%)
    9 / 38 (23.68%)
    5 / 22 (22.73%)
         occurrences all number
    5
    4
    4
    35
    13
    11
    Thrombocytopenia
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    3 / 8 (37.50%)
    5 / 40 (12.50%)
    6 / 38 (15.79%)
    1 / 22 (4.55%)
         occurrences all number
    20
    1
    11
    6
    10
    1
    Splenomegaly
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pancytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    0
    Neutropenia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    4 / 8 (50.00%)
    19 / 40 (47.50%)
    14 / 38 (36.84%)
    7 / 22 (31.82%)
         occurrences all number
    1
    0
    6
    30
    24
    11
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    1
    0
    1
    Halo vision
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Retinopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    0
    Gastrointestinal disorders
    Colonic haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    8 / 40 (20.00%)
    6 / 38 (15.79%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    2
    9
    6
    1
    Anal incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    6 / 38 (15.79%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    3
    7
    0
    Dry mouth
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    6 / 40 (15.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    7
    0
    1
    Diarrhoea
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    12 / 40 (30.00%)
    12 / 38 (31.58%)
    4 / 22 (18.18%)
         occurrences all number
    3
    1
    2
    14
    17
    6
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
    14 / 40 (35.00%)
    6 / 38 (15.79%)
    4 / 22 (18.18%)
         occurrences all number
    0
    2
    3
    17
    6
    4
    Lip dry
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oral pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    Nausea
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    6 / 8 (75.00%)
    22 / 40 (55.00%)
    17 / 38 (44.74%)
    9 / 22 (40.91%)
         occurrences all number
    1
    1
    7
    33
    24
    10
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    6 / 40 (15.00%)
    3 / 38 (7.89%)
    2 / 22 (9.09%)
         occurrences all number
    1
    0
    1
    9
    3
    2
    Vomiting
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    11 / 40 (27.50%)
    9 / 38 (23.68%)
    5 / 22 (22.73%)
         occurrences all number
    2
    0
    4
    18
    11
    7
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Alopecia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    12 / 40 (30.00%)
    7 / 38 (18.42%)
    9 / 22 (40.91%)
         occurrences all number
    2
    2
    0
    12
    7
    9
    Dry skin
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    1
    3
    1
    1
    Ecchymosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Nail disorder
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 40 (5.00%)
    4 / 38 (10.53%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    2
    4
    1
    Rash
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    6 / 38 (15.79%)
    4 / 22 (18.18%)
         occurrences all number
    1
    0
    0
    5
    8
    4
    Rash maculo-papular
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    2
    0
    2
    2
    1
    Urticaria
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    2
    1
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Acute kidney injury
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    1
    0
    2
    2
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Micturition urgency
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    1
    2
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 40 (7.50%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    3
    3
    2
    2
    Arthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 40 (7.50%)
    5 / 38 (13.16%)
    3 / 22 (13.64%)
         occurrences all number
    0
    1
    1
    3
    5
    3
    Muscle spasms
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    Muscular weakness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    1 / 38 (2.63%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    0
    4
    1
    3
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    3
    2
    1
    2
    Neck pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    Skin candida
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Pseudomonal bacteraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    Oral candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    2
    3
    0
    1
    Influenza
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    4 / 40 (10.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    4
    1
    0
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    1 / 40 (2.50%)
    3 / 38 (7.89%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    2
    2
    4
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    4 / 8 (50.00%)
    15 / 40 (37.50%)
    11 / 38 (28.95%)
    1 / 22 (4.55%)
         occurrences all number
    2
    4
    4
    17
    13
    1
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    2 / 38 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    4
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    4 / 40 (10.00%)
    2 / 38 (5.26%)
    3 / 22 (13.64%)
         occurrences all number
    0
    0
    1
    5
    3
    4
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 40 (2.50%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    0
    1
    2
    1
    Hypervolaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    6 / 40 (15.00%)
    2 / 38 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    2
    14
    4
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    6 / 40 (15.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    8
    1
    0
    Hypomagnesaemia
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    5 / 8 (62.50%)
    6 / 40 (15.00%)
    4 / 38 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    8
    6
    5
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    2 / 40 (5.00%)
    3 / 38 (7.89%)
    2 / 22 (9.09%)
         occurrences all number
    3
    1
    2
    9
    3
    2
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    7 / 40 (17.50%)
    4 / 38 (10.53%)
    1 / 22 (4.55%)
         occurrences all number
    0
    0
    1
    12
    6
    1
    Metabolic acidosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    5 / 8 (62.50%)
    13 / 40 (32.50%)
    4 / 38 (10.53%)
    1 / 22 (4.55%)
         occurrences all number
    1
    3
    13
    25
    4
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Aug 2018
    Replaced Pola-M-CHP in first-line DLBCL with a safety run-in group of M-CHOP in first-line DLBCL. ADA objectives added to secondary objectives.
    27 Oct 2018
    Updated starting test dose for Group A. Updated inclusion criteria.
    27 May 2020
    Updates to eligibility criteria.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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