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A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01992653
Collaborator
(none)
85
Enrollment
11
Locations
8
Arms
60.6
Actual Duration (Months)
7.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
85 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma
Actual Study Start Date :
Nov 29, 2013
Actual Primary Completion Date :
Dec 19, 2018
Actual Study Completion Date :
Dec 19, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Polatuzumab Vedotin (1.4mg) + G-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Drug: Cyclophosphamide
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Drug: Doxorubicin
Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Drug: Obinutuzumab
Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
Other Names:
  • Gazyva/Gazyvaro

    • Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
    Experimental: Polatuzumab Vedotin (1.0mg) + R-CHP

    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Names:
  • MabThera/Rituxan

    		•
    Experimental: Polatuzumab Vedotin (1.8mg) + G-CHP

    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Obinutuzumab
    Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
    Other Names:
  • Gazyva/Gazyvaro

    • Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
    Experimental: Polatuzumab Vedotin (1.4mg) + R-CHP

    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Names:
  • MabThera/Rituxan

    		•
    Experimental: Polatuzumab Vedotin (1.8mg) + R-CHP

    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Names:
  • MabThera/Rituxan

    		•
    Experimental: Polatuzumab Vedotin (2.4mg) + R-CHP

    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Names:
  • MabThera/Rituxan

    		•
    Experimental: Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP

    Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Names:
  • MabThera/Rituxan

    		•
    Experimental: Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP

    Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

    Drug: Cyclophosphamide
    Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

    Drug: Obinutuzumab
    Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
    Other Names:
  • Gazyva/Gazyvaro

    • Drug: Polatuzumab Vedotin
    Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
    Other Names:
  • DCDS4501A

    • Drug: Prednisolone
    Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Drug: Prednisone
    Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population [Baseline up to 5 years]

      An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).

    2. Number of Participants With Adverse Events in Non-DLBCL Population [Baseline up to 5 years]

      An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).

    3. Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population [Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)]

      All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.

    4. Number of Participants With DLTs in Non-DLBCL Population [Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)]

      All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.

    Secondary Outcome Measures

    1. Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population [At the end of treatment (Month 6)]

      Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.

    2. Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population [At the end of treatment (Month 6)]

      Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.

    3. Number of Participants With Anti-Polatuzumab Vedotin Antibodies [Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days)]

      The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 μg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 μg/mL. Polatuzumab vedotin total antibody concentrations ranged from <0.050 μg/mL to 52.1 μg/mL with a median concentration of 3.38 μg/mL.

    4. Number of Participants With Anti-Obinutuzumab Antibodies [Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days)]

      The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA.

    5. Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin [Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)]

      AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

    6. Maximum Concentration (Cmax) of Polatuzumab Vedotin [Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)]

      Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

    7. Clearance (CL) of Polatuzumab Vedotin [Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)]

      CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

    8. Terminal Half-Life (t1/2) of Polatuzumab Vedotin [Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)]

      t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

    9. Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin [Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)]

      Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

    10. Plasma Levels of Cyclophosphamide [End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days)]

      Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.

    11. Plasma Levels of Doxorubicin [2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days)]

      Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.

    12. Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score [Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.]

      The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).

    13. Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score [Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.]

      The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).

    14. Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.

    15. Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.

    16. Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.

    17. Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.

    18. Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.

    19. Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population [Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)]

      Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.

    20. Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population [6 months]

      Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.

    21. Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population [6 months]

      Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.

    22. Overall Survival for DLBCL Population [Screening up to death due to any cause (up to approximately 6 years)]

      The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.

    23. Overall Survival for Non-DLBCL Population [Screening up to death due to any cause (up to approximately 6 years)]

      The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    All Participants:

    • At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeters (cm) in its longest dimension

    • Life expectancy of at least 24 weeks

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

    • Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)

    • Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of <1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug

    Dose-Escalation Portion of the Study:

    • Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible

    • No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation [CD] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen)

    • No prior treatment with anthracyclines

    Expansion Portion of the Study:

    • Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)

    • International Prognostic Index (IPI) score of 2-5

    Exclusion Criteria:
    Dose-Escalation Portion of the Study:
    • Diagnosis of primary mediastinal DLBCL
    Expansion Portion of the Study:

    • Participants with transformed lymphoma

    • Prior therapy for NHL

    All Participants:

    • Prior stem cell transplant

    • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

    • Contraindication to receive any of the individual components of R-CHP or G-CHP

    • Current Grade greater than (>) 1 peripheral neuropathy

    • Ongoing corticosteroid use of >30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1

    • Primary central nervous system (CNS) lymphoma

    • Vaccination with live vaccines within 6 months before Cycle 1 Day 1

    • History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (</=) 5 years before enrollment

    • Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)

    • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease

    • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1

    • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

    • Positive for hepatitis B or hepatitis C infection

    • Prior radiotherapy to the mediastinal/pericardial region

    • Pregnant or lactating women

    • Recent major surgery within 6 weeks before the start of Cycle 1 Day 1

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    3 Washington University; Pediatrics Saint Louis Missouri United States 63110
    4 Northwest Cancer Specialists Portland Oregon United States 97210
    5 Oregon Health and Science University Portland Oregon United States 97239
    6 Willamette Valley Clinical Studies; Cancer Institute Springfield Oregon United States 97477
    7 Blue Ridge Cancer Care Roanoke Virginia United States 24014
    8 Hopital Henri Mondor, Unite Hemopathies lymphoides Creteil France 94010
    9 Hopital Claude Huriez - CHU Lille; Service des maladies du sang Lille France 59037
    10 Centre Hospitalier Lyon Sud; Hematolgie Pierre Benite France 69495
    11 Centre Henri Becquerel; Hematologie Rouen France 76038

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Genentech, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT01992653
    Other Study ID Numbers:
    • GO29044
    • 2013-003541-42
    First Posted:
    Nov 25, 2013
    Last Update Posted:
    Mar 3, 2020
    Last Verified:
    Feb 1, 2020
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell
    Prednisone
    Prednisolone
    Cyclophosphamide
    Rituximab
    Doxorubicin
    Obinutuzumab

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 11 centers in 2 countries.
    Pre-assignment Detail A total of 85 participants were enrolled at 11 centers in the following countries: France (31 participants) and United States (54 participants). 3 participants did not receive any study treatment (2 had exclusionary lab values and 1 withdrew) meaning that the safety population consisted of 82 participants.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Period Title: Overall Study
    STARTED 3 3 6 1 6 6 40 17
    COMPLETED 3 3 5 1 5 6 32 13
    NOT COMPLETED 0 0 1 0 1 0 8 4

    Baseline Characteristics

    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP Total
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts. Total of all reporting groups
    Overall Participants 3 3 6 1 6 6 40 17 82
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    67.3
    (6.4)
    65.0
    (7.0)
    67.3
    (3.5)
    68.0
    (NA)
    70.7
    (4.5)
    60.0
    (14.3)
    69.6
    (7.2)
    61.6
    (14.6)
    66.9
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    3
    100%
    4
    66.7%
    0
    0%
    2
    33.3%
    4
    66.7%
    20
    50%
    6
    35.3%
    39
    47.6%
    Male
    3
    100%
    0
    0%
    2
    33.3%
    1
    100%
    4
    66.7%
    2
    33.3%
    20
    50%
    11
    64.7%
    43
    52.4%
    Race/Ethnicity, Customized (Number) [Number]
    Not Hispanic or Latino
    3
    100%
    3
    100%
    6
    100%
    1
    100%
    6
    100%
    6
    100%
    27
    67.5%
    14
    82.4%
    66
    80.5%
    Not Stated
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    22.5%
    3
    17.6%
    12
    14.6%
    Unknown
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    10%
    0
    0%
    4
    4.9%
    Race/Ethnicity, Customized (Number) [Number]
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    1
    5.9%
    2
    2.4%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    10%
    1
    5.9%
    5
    6.1%
    Unknown
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    7.5%
    0
    0%
    3
    3.7%
    White
    3
    100%
    3
    100%
    6
    100%
    1
    100%
    5
    83.3%
    6
    100%
    33
    82.5%
    15
    88.2%
    72
    87.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population
    Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
    Time Frame Baseline up to 5 years

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    82
    2
    66.7%
    3
    100%
    5
    83.3%
    0
    0%
    4
    66.7%
    4
    66.7%
    40
    100%
    17
    100%
    2. Primary Outcome
    Title Number of Participants With Adverse Events in Non-DLBCL Population
    Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
    Time Frame Baseline up to 5 years

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    82
    1
    33.3%
    0
    0%
    1
    16.7%
    1
    100%
    2
    33.3%
    2
    33.3%
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population
    Description All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
    Time Frame Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 0 0
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    4. Primary Outcome
    Title Number of Participants With DLTs in Non-DLBCL Population
    Description All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
    Time Frame Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5. Secondary Outcome
    Title Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population
    Description Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.
    Time Frame At the end of treatment (Month 6)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Complete Response (CR)
    50.0
    1666.7%
    100.0
    3333.3%
    100.0
    1666.7%
    75.0
    7500%
    100.0
    1666.7%
    75.0
    1250%
    76.5
    191.3%
    Partial Response (PR)
    50.0
    1666.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    15.0
    250%
    11.8
    29.5%
    6. Secondary Outcome
    Title Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
    Description Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.
    Time Frame At the end of treatment (Month 6)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Complete Response (CR)
    100.0
    3333.3%
    100.0
    3333.3%
    100.0
    1666.7%
    100.0
    10000%
    100.0
    1666.7%
    Partial Response (PR)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Number of Participants With Anti-Polatuzumab Vedotin Antibodies
    Description The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 μg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 μg/mL. Polatuzumab vedotin total antibody concentrations ranged from <0.050 μg/mL to 52.1 μg/mL with a median concentration of 3.38 μg/mL.
    Time Frame Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Number of Participants With Anti-Obinutuzumab Antibodies
    Description The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA.
    Time Frame Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin
    Description AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
    Time Frame Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Mean (Standard Deviation) [ng day/mL]
    1300
    (22)
    1510
    (354)
    2600
    (413)
    4090
    (NA)
    1940
    (154)
    1850
    (491)
    1870
    (527)
    1940
    (482)
    10. Secondary Outcome
    Title Maximum Concentration (Cmax) of Polatuzumab Vedotin
    Description Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
    Time Frame Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Mean (Standard Deviation) [ng/mL]
    373
    (147)
    537
    (184)
    781
    (72.6)
    1400
    (NA)
    537
    (59.1)
    557
    (114)
    532
    (163)
    530
    (138)
    11. Secondary Outcome
    Title Clearance (CL) of Polatuzumab Vedotin
    Description CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
    Time Frame Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Mean (Standard Deviation) [mL/day/kg]
    14.0
    (0.370)
    17.3
    (4.16)
    12.8
    (2.05)
    10.5
    (NA)
    13.2
    (1.29)
    18.7
    (5.30)
    18.9
    (5.27)
    17.7
    (3.83)
    12. Secondary Outcome
    Title Terminal Half-Life (t1/2) of Polatuzumab Vedotin
    Description t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
    Time Frame Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Mean (Standard Deviation) [days]
    5.03
    (0.905)
    4.85
    (0.720)
    4.79
    (0.675)
    4.42
    (NA)
    5.19
    (0.430)
    4.89
    (0.526)
    5.03
    (0.621)
    5.50
    (0.795)
    13. Secondary Outcome
    Title Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin
    Description Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
    Time Frame Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 3 3 6 1 6 6 40 17
    Mean (Standard Deviation) [mL/kg]
    58.2
    (9.92)
    80.0
    (9.97)
    57.7
    (7.95)
    41.9
    (NA)
    67.9
    (7.42)
    87.5
    (19.3)
    96.5
    (34.1)
    99.3
    (27.4)
    14. Secondary Outcome
    Title Plasma Levels of Cyclophosphamide
    Description Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.
    Time Frame End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of cyclophosphamide were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 0 0 0 0 0 0 40 17
    C1D1 0.5hr POSTDOSE
    37.5
    (24.4)
    32.3
    (7.64)
    C1D1 3.5hr POSTDOSE
    23.2
    (2.38)
    22.5
    (3.69)
    C1D1 23.5hr POSTDOSE
    2.98
    (1.39)
    3.32
    (1.50)
    C3D1 0.5hr POSTDOSE
    34.8
    (6.14)
    35.2
    (13.4)
    C3D1 3.5hr POSTDOSE
    24.2
    (3.87)
    22.5
    (4.26)
    C3D1 23.5hr POSTDOSE
    3.17
    (1.66)
    3.16
    (1.68)
    15. Secondary Outcome
    Title Plasma Levels of Doxorubicin
    Description Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.
    Time Frame 2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of doxorubicin were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 0 0 0 0 0 0 40 17
    C1D1 2hr POSTDOSE
    35.4
    (13.6)
    30.2
    (6.82)
    C1D1 24hr POSTDOSE
    9.13
    (2.51)
    11.7
    (11.6)
    C3D1 2hr POSTDOSE
    29.3
    (10.9)
    29.6
    (10.8)
    C3D1 24hr POSTDOSE
    8.68
    (2.05)
    9.14
    (2.12)
    16. Secondary Outcome
    Title Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score
    Description The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).
    Time Frame Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. TINAS was only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 0 0 0 0 0 0 40 17
    Baseline
    0
    (NA)
    0.32
    (0.45)
    Week 1
    0
    (0)
    0.91
    (0.92)
    Week 2
    0.02
    (0.04)
    0.07
    (0.16)
    Week 3
    0.06
    (0.10)
    0.22
    (0.44)
    Week 4
    0.18
    (0.36)
    0.26
    (0.63)
    Week 5
    0.16
    (0.32)
    0.17
    (0.41)
    Week 6
    0.16
    (0.32)
    0.25
    (0.57)
    Week 7
    0.14
    (0.28)
    0.35
    (0.77)
    Week 8
    0.17
    (0.37)
    0.31
    (0.59)
    Week 9
    0.25
    (0.47)
    0.38
    (0.61)
    Week 10
    0.30
    (0.41)
    0.53
    (0.71)
    Week 11
    0.26
    (0.35)
    0.39
    (0.73)
    Week 12
    0.30
    (0.43)
    0.65
    (1.02)
    Week 13
    0.25
    (0.32)
    0.78
    (1.34)
    Week 14
    0.49
    (0.86)
    0.62
    (1.05)
    Week 15
    0.48
    (0.86)
    0.70
    (1.28)
    Week 16
    0.66
    (0.94)
    1.12
    (1.61)
    Week 17
    0.25
    (0.52)
    0.91
    (1.44)
    Week 18
    0.64
    (NA)
    Week 19
    0.45
    (NA)
    Week 22
    0.09
    (NA)
    17. Secondary Outcome
    Title Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score
    Description The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).
    Time Frame Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected.

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. TINAS was only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 0 0 0 0 0 0 40 17
    Baseline
    0
    (NA)
    0
    (0)
    Week 1
    0
    (0)
    1
    (1.73)
    Week 2
    0.25
    (0.50)
    0
    (0)
    Week 3
    0.33
    (0.58)
    0.40
    (0.89)
    Week 4
    0.40
    (0.55)
    0.50
    (1.22)
    Week 5
    0.40
    (0.55)
    0.17
    (0.41)
    Week 6
    0.40
    (0.55)
    0.40
    (0.89)
    Week 7
    0.29
    (0.49)
    0.60
    (1.34)
    Week 8
    0.33
    (0.52)
    0.25
    (0.71)
    Week 9
    0.40
    (0.55)
    0.50
    (1.07)
    Week 10
    0.86
    (1.21)
    1.14
    (1.46)
    Week 11
    0.86
    (1.21)
    0.57
    (1.13)
    Week 12
    1.14
    (1.21)
    0.71
    (1.25)
    Week 13
    0.86
    (1.21)
    1.12
    (1.81)
    Week 14
    1.12
    (1.73)
    0.88
    (1.36)
    Week 15
    1.12
    (1.73)
    0.75
    (1.16)
    Week 16
    1.56
    (2.07)
    1.50
    (1.69)
    Week 17
    0.40
    (0.55)
    1.14
    (1.46)
    Week 18
    2
    (NA)
    Week 19
    2
    (NA)
    Week 22
    1
    (NA)
    18. Secondary Outcome
    Title Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
    Description Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    19. Secondary Outcome
    Title Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
    Description Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Median (95% Confidence Interval) [Months]
    NA
    4.11
    NA
    NA
    NA
    20. Secondary Outcome
    Title Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
    Description Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    21. Secondary Outcome
    Title Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
    Description Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Median (95% Confidence Interval) [Months]
    NA
    6.87
    NA
    NA
    NA
    22. Secondary Outcome
    Title Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
    Description Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    NA
    NA
    35.45
    NA
    23. Secondary Outcome
    Title Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
    Description Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.
    Time Frame Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Median (95% Confidence Interval) [Months]
    NA
    6.87
    6.70
    NA
    NA
    24. Secondary Outcome
    Title Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population
    Description Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Mean (Standard Deviation) [Percentage]
    100.70
    (0.99)
    99.97
    (0.55)
    96.04
    (4.81)
    99.35
    (3.19)
    99.95
    (0.75)
    96.71
    (6.99)
    98.92
    (3.74)
    25. Secondary Outcome
    Title Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population
    Description Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Mean (Standard Deviation) [Percentage]
    100.00
    (NA)
    100.94
    (NA)
    132.22
    (NA)
    99.72
    (0.06)
    100.17
    (0.14)
    26. Secondary Outcome
    Title Overall Survival for DLBCL Population
    Description The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.
    Time Frame Screening up to death due to any cause (up to approximately 6 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 2 3 5 0 4 4 40 17
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    27. Secondary Outcome
    Title Overall Survival for Non-DLBCL Population
    Description The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.
    Time Frame Screening up to death due to any cause (up to approximately 6 years)

    Outcome Measure Data

    Analysis Population Description
    The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    Measure Participants 1 0 1 1 2 2 0 0
    Median (95% Confidence Interval) [Months]
    NA
    15.24
    NA
    NA
    NA

    Adverse Events

    Time Frame 5 years
    Adverse Event Reporting Description The safety population was defined as all participants who received at least one dose of study medication. AEs that were entered into the data base at the time of the data base lock were included in the AE analysis.
    Arm/Group Title Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Arm/Group Description Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts. Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.
    All Cause Mortality
    Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/1 (0%) 1/6 (16.7%) 0/6 (0%) 4/40 (10%) 2/17 (11.8%)
    Serious Adverse Events
    Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 1/3 (33.3%) 4/6 (66.7%) 0/1 (0%) 1/6 (16.7%) 3/6 (50%) 15/40 (37.5%) 6/17 (35.3%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 0/3 (0%) 0 1/3 (33.3%) 2 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 2/6 (33.3%) 3 3/40 (7.5%) 4 4/17 (23.5%) 4
    NEUTROPENIA 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 3 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    THROMBOCYTOPENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Cardiac disorders
    ATRIAL FIBRILLATION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 2/40 (5%) 2 0/17 (0%) 0
    CORONARY ARTERY DISEASE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    SUPRAVENTRICULAR TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    Gastrointestinal disorders
    DIARRHOEA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    DYSPHAGIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    VOMITING 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    General disorders
    ASTHENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    Infections and infestations
    CLOSTRIDIUM DIFFICILE INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2 0/40 (0%) 0 0/17 (0%) 0
    ESCHERICHIA URINARY TRACT INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    LUNG INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    ORAL FUNGAL INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    PNEUMONIA 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    SEPSIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    SEPTIC SHOCK 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Injury, poisoning and procedural complications
    FEMUR FRACTURE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    INFUSION RELATED REACTION 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PELVIC FRACTURE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    Investigations
    INFLUENZA A VIRUS TEST POSITIVE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 2 0/17 (0%) 0
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    HYPONATRAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    MALNUTRITION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    Musculoskeletal and connective tissue disorders
    ARTHRITIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    RHEUMATOID ARTHRITIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    Nervous system disorders
    SYNCOPE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 1/40 (2.5%) 1 0/17 (0%) 0
    Psychiatric disorders
    ANXIETY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    MENTAL STATUS CHANGES 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    CHYLOTHORAX 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    PULMONARY EMBOLISM 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    Other (Not Including Serious) Adverse Events
    Polatuzumab Vedotin (1.0mg) + R-CHP Polatuzumab Vedotin (1.4mg) + R-CHP Polatuzumab Vedotin (1.8mg) + R-CHP Polatuzumab Vedotin (2.4mg) + R-CHP Polatuzumab Vedotin (1.4mg) + G-CHP Polatuzumab Vedotin (1.8mg) + G-CHP Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 6/6 (100%) 1/1 (100%) 6/6 (100%) 6/6 (100%) 40/40 (100%) 17/17 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 3/6 (50%) 4 2/6 (33.3%) 5 14/40 (35%) 24 3/17 (17.6%) 7
    FEBRILE NEUTROPENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 3/40 (7.5%) 3 1/17 (5.9%) 1
    LEUKOCYTOSIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 6/40 (15%) 9 3/17 (17.6%) 4
    LEUKOPENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 7/40 (17.5%) 16 2/17 (11.8%) 2
    NEUTROPENIA 1/3 (33.3%) 1 0/3 (0%) 0 4/6 (66.7%) 8 0/1 (0%) 0 3/6 (50%) 3 5/6 (83.3%) 5 13/40 (32.5%) 22 6/17 (35.3%) 9
    PANCYTOPENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2 0/40 (0%) 0 1/17 (5.9%) 1
    THROMBOCYTOPENIA 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 3 1/6 (16.7%) 2 6/40 (15%) 16 6/17 (35.3%) 6
    Cardiac disorders
    PALPITATIONS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    SUPRAVENTRICULAR TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 2/40 (5%) 2 2/17 (11.8%) 3
    Ear and labyrinth disorders
    CERUMEN IMPACTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    EAR DISCOMFORT 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    EAR PAIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    EXCESSIVE CERUMEN PRODUCTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    HYPOACUSIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    MIDDLE EAR EFFUSION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Eye disorders
    AMBLYOPIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    CATARACT 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    CONJUNCTIVAL HYPERAEMIA 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    CONJUNCTIVAL IRRITATION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    DIPLOPIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    EYE IRRITATION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    LACRIMATION INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 2 2/17 (11.8%) 2
    ABDOMINAL PAIN UPPER 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 3/40 (7.5%) 4 0/17 (0%) 0
    COLITIS MICROSCOPIC 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    CONSTIPATION 1/3 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 2/6 (33.3%) 2 11/40 (27.5%) 14 5/17 (29.4%) 5
    DIARRHOEA 1/3 (33.3%) 1 0/3 (0%) 0 5/6 (83.3%) 7 1/1 (100%) 1 2/6 (33.3%) 4 2/6 (33.3%) 2 17/40 (42.5%) 25 11/17 (64.7%) 14
    DRY MOUTH 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 1/40 (2.5%) 1 1/17 (5.9%) 1
    DYSPEPSIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 2 1/17 (5.9%) 2
    DYSPHAGIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 3/40 (7.5%) 3 1/17 (5.9%) 1
    ERUCTATION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    FLATULENCE 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    GASTROINTESTINAL MOTILITY DISORDER 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    GASTROOESOPHAGEAL REFLUX DISEASE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 2/17 (11.8%) 2
    HAEMATOCHEZIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    HAEMORRHOIDS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    HYPERCHLORHYDRIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    NAUSEA 1/3 (33.3%) 1 3/3 (100%) 5 4/6 (66.7%) 7 1/1 (100%) 1 3/6 (50%) 3 3/6 (50%) 3 16/40 (40%) 26 10/17 (58.8%) 12
    ORAL PAIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    SMALL INTESTINAL OBSTRUCTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    STOMATITIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 1/40 (2.5%) 1 1/17 (5.9%) 1
    VOMITING 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 6/40 (15%) 8 3/17 (17.6%) 4
    General disorders
    ASTHENIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 9/40 (22.5%) 12 1/17 (5.9%) 4
    CATHETER SITE PAIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    CHEST DISCOMFORT 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    CHEST PAIN 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 3/40 (7.5%) 3 1/17 (5.9%) 1
    CHILLS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 4/40 (10%) 4 3/17 (17.6%) 3
    DEVICE RELATED THROMBOSIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    FACE OEDEMA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 2
    FATIGUE 2/3 (66.7%) 2 3/3 (100%) 4 3/6 (50%) 3 1/1 (100%) 1 1/6 (16.7%) 1 4/6 (66.7%) 4 16/40 (40%) 29 11/17 (64.7%) 16
    FEELING HOT 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    GAIT DISTURBANCE 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    ILL-DEFINED DISORDER 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    MUCOSAL INFLAMMATION 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 3 0/17 (0%) 0
    NON-CARDIAC CHEST PAIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    OEDEMA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    OEDEMA PERIPHERAL 0/3 (0%) 0 1/3 (33.3%) 2 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 2/6 (33.3%) 2 4/40 (10%) 4 3/17 (17.6%) 3
    PAIN 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 4/40 (10%) 5 1/17 (5.9%) 1
    PERIPHERAL SWELLING 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 1/40 (2.5%) 1 0/17 (0%) 0
    PYREXIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 3 9/40 (22.5%) 11 4/17 (23.5%) 4
    Hepatobiliary disorders
    HEPATIC STEATOSIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Immune system disorders
    SEASONAL ALLERGY 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Infections and infestations
    BACTERAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    BRONCHITIS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 7/40 (17.5%) 10 2/17 (11.8%) 2
    CANDIDA INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 3/40 (7.5%) 3 0/17 (0%) 0
    CONJUNCTIVITIS VIRAL 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    CYSTITIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    ESCHERICHIA URINARY TRACT INFECTION 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    FOLLICULITIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    FUNGAL INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    NASOPHARYNGITIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    OPHTHALMIC HERPES ZOSTER 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    ORAL CANDIDIASIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    OTITIS MEDIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PNEUMONIA 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    RASH PUSTULAR 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    SINUSITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2 0/40 (0%) 0 2/17 (11.8%) 3
    SUBCUTANEOUS ABSCESS 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    URINARY TRACT INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 4/40 (10%) 4 0/17 (0%) 0
    VASCULAR DEVICE INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 1/40 (2.5%) 1 3/17 (17.6%) 4
    MEDICATION ERROR 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    POST LUMBAR PUNCTURE SYNDROME 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 4 0/17 (0%) 0
    PROCEDURAL HEADACHE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 3 0/17 (0%) 0
    ASPARTATE AMINOTRANSFERASE INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    BLOOD CREATININE INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 2/17 (11.8%) 2
    BLOOD LACTIC ACID INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    BLOOD PHOSPHORUS DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    BLOOD POTASSIUM DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    EJECTION FRACTION DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    NEUTROPHIL COUNT DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PLATELET COUNT DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 2 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    STAPHYLOCOCCUS TEST POSITIVE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    STREPTOCOCCUS TEST POSITIVE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    TRANSAMINASES INCREASED 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    TROPONIN I INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    TROPONIN INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 2/17 (11.8%) 2
    WEIGHT DECREASED 0/3 (0%) 0 0/3 (0%) 0 3/6 (50%) 3 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 6/40 (15%) 6 5/17 (29.4%) 6
    WHITE BLOOD CELL COUNT DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 3/40 (7.5%) 4 1/17 (5.9%) 2
    WHITE BLOOD CELL COUNT INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Metabolism and nutrition disorders
    DECREASED APPETITE 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 5/40 (12.5%) 7 2/17 (11.8%) 3
    DEHYDRATION 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 1/6 (16.7%) 3 1/40 (2.5%) 1 1/17 (5.9%) 1
    HYPERGLYCAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 5/40 (12.5%) 7 1/17 (5.9%) 2
    HYPERNATRAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    HYPERURICAEMIA 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    HYPOALBUMINAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    HYPOCALCAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    HYPOKALAEMIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 3/40 (7.5%) 6 4/17 (23.5%) 5
    HYPOMAGNESAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2 0/40 (0%) 0 2/17 (11.8%) 2
    HYPONATRAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 1/40 (2.5%) 3 1/17 (5.9%) 1
    HYPOPHOSPHATAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 3/40 (7.5%) 4 0/17 (0%) 0
    MALNUTRITION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 4/40 (10%) 4 0/17 (0%) 0
    BACK PAIN 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 3/40 (7.5%) 3 4/17 (23.5%) 5
    BONE PAIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 1/6 (16.7%) 1 4/40 (10%) 5 2/17 (11.8%) 2
    MUSCLE SPASMS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 1/40 (2.5%) 2 1/17 (5.9%) 1
    MUSCLE TIGHTNESS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    MUSCULOSKELETAL CHEST PAIN 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    MUSCULOSKELETAL PAIN 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PAIN IN EXTREMITY 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 2/17 (11.8%) 2
    SYNOVIAL CYST 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    Nervous system disorders
    BALANCE DISORDER 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    DIZZINESS 1/3 (33.3%) 1 2/3 (66.7%) 5 2/6 (33.3%) 2 1/1 (100%) 1 2/6 (33.3%) 2 0/6 (0%) 0 3/40 (7.5%) 3 3/17 (17.6%) 3
    DYSGEUSIA 0/3 (0%) 0 1/3 (33.3%) 1 2/6 (33.3%) 2 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 3/40 (7.5%) 3 3/17 (17.6%) 3
    DYSTONIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    ENCEPHALOPATHY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    HEADACHE 1/3 (33.3%) 1 2/3 (66.7%) 2 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 2/6 (33.3%) 2 4/40 (10%) 5 1/17 (5.9%) 1
    HYPOAESTHESIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 0/40 (0%) 0 0/17 (0%) 0
    HYPOGEUSIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    MEMORY IMPAIRMENT 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    NEURALGIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    NEUROPATHY PERIPHERAL 1/3 (33.3%) 1 1/3 (33.3%) 1 1/6 (16.7%) 1 1/1 (100%) 3 2/6 (33.3%) 3 2/6 (33.3%) 3 5/40 (12.5%) 7 2/17 (11.8%) 2
    PARAESTHESIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 4/40 (10%) 5 1/17 (5.9%) 1
    PERIPHERAL MOTOR NEUROPATHY 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PERIPHERAL SENSORIMOTOR NEUROPATHY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    PERIPHERAL SENSORY NEUROPATHY 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 6/40 (15%) 6 3/17 (17.6%) 4
    SCIATICA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 3 0/17 (0%) 0
    SOMNOLENCE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    SYNCOPE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 3 1/17 (5.9%) 1
    TREMOR 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 2 0/17 (0%) 0
    Psychiatric disorders
    AFFECT LABILITY 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    ANXIETY 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 1/6 (16.7%) 1 4/40 (10%) 4 2/17 (11.8%) 3
    CONFUSIONAL STATE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 1/17 (5.9%) 1
    DEPRESSION 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 1/17 (5.9%) 1
    INSOMNIA 1/3 (33.3%) 1 2/3 (66.7%) 2 2/6 (33.3%) 2 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 5/40 (12.5%) 5 3/17 (17.6%) 3
    IRRITABILITY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    MENTAL STATUS CHANGES 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    MOOD ALTERED 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    NIGHTMARE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    RESTLESSNESS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 3 0/40 (0%) 0 0/17 (0%) 0
    DYSURIA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/6 (16.7%) 1 1/6 (16.7%) 1 1/40 (2.5%) 1 0/17 (0%) 0
    HAEMATURIA 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    POLLAKIURIA 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 0/40 (0%) 0 0/17 (0%) 0
    RENAL COLIC 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    RENAL FAILURE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 2
    RENAL IMPAIRMENT 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    URINARY INCONTINENCE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    URINARY RETENTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    URINE FLOW DECREASED 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Reproductive system and breast disorders
    PELVIC PAIN 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    TESTICULAR OEDEMA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    VAGINAL DISCHARGE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    ATELECTASIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    COUGH 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 1/6 (16.7%) 1 3/6 (50%) 4 1/40 (2.5%) 1 2/17 (11.8%) 3
    DYSPHONIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 2/17 (11.8%) 2
    DYSPNOEA 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 2/6 (33.3%) 4 3/40 (7.5%) 5 1/17 (5.9%) 1
    DYSPNOEA EXERTIONAL 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 1/40 (2.5%) 1 0/17 (0%) 0
    EPISTAXIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    HYPOXIA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 1/17 (5.9%) 1
    LOWER RESPIRATORY TRACT CONGESTION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 0/40 (0%) 0 1/17 (5.9%) 1
    OROPHARYNGEAL PAIN 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 1/40 (2.5%) 1 2/17 (11.8%) 2
    PARANASAL SINUS HYPERSECRETION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 3/6 (50%) 3 0/40 (0%) 0 0/17 (0%) 0
    PLEURAL EFFUSION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    PRODUCTIVE COUGH 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 3 0/17 (0%) 0
    PULMONARY OEDEMA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    RHINITIS ALLERGIC 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    RHINORRHOEA 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    TACHYPNOEA 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    THROAT IRRITATION 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    THROAT TIGHTNESS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    UPPER-AIRWAY COUGH SYNDROME 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 2/40 (5%) 2 0/17 (0%) 0
    Skin and subcutaneous tissue disorders
    ALOPECIA 1/3 (33.3%) 1 1/3 (33.3%) 1 1/6 (16.7%) 1 0/1 (0%) 0 5/6 (83.3%) 5 4/6 (66.7%) 4 4/40 (10%) 7 4/17 (23.5%) 5
    DERMATITIS CONTACT 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    ERYTHEMA 1/3 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 1/40 (2.5%) 1 2/17 (11.8%) 2
    HYPERHIDROSIS 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    NAIL RIDGING 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    NIGHT SWEATS 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2 2/40 (5%) 2 1/17 (5.9%) 1
    PAIN OF SKIN 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    PAPULE 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    PRURITUS 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 1/17 (5.9%) 1
    RASH 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 1/6 (16.7%) 1 3/6 (50%) 3 1/40 (2.5%) 1 0/17 (0%) 0
    RASH MACULO-PAPULAR 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    Vascular disorders
    DEEP VEIN THROMBOSIS 1/3 (33.3%) 1 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    EMBOLISM 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0
    FLUSHING 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/6 (0%) 0 1/6 (16.7%) 1 1/40 (2.5%) 1 0/17 (0%) 0
    HOT FLUSH 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/40 (0%) 0 0/17 (0%) 0
    HYPERTENSION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/6 (16.7%) 2 0/6 (0%) 0 7/40 (17.5%) 16 1/17 (5.9%) 2
    HYPOTENSION 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 2/6 (33.3%) 2 0/6 (0%) 0 2/40 (5%) 2 1/17 (5.9%) 1
    PHLEBITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/40 (0%) 0 0/17 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800 821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT01992653
    Other Study ID Numbers:
    • GO29044
    • 2013-003541-42
    First Posted:
    Nov 25, 2013
    Last Update Posted:
    Mar 3, 2020
    Last Verified:
    Feb 1, 2020