A Study of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus (+) Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Follicular Lymphoma (FL) or Rituximab + CHOP in Participants With Diffuse Large B-Cell Lymphoma (DLBCL)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02596971
Collaborator
(none)
91
Enrollment
21
Locations
3
Arms
52.5
Actual Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and atezolizumab + rituximab + chemotherapy (Atezo-R-CHOP) in participants with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in participants with FL who achieve a complete response (CR) or partial response (PR) at end of induction (EOI) or atezolizumab alone in participants with DLBCL who achieve a CR at EOI.

Study Design

Study Type:
Interventional
Actual Enrollment :
91 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 and Efficacy of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus CHOP in Patients With Follicular Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-Cell Lymphoma
Actual Study Start Date :
Dec 22, 2015
Actual Primary Completion Date :
Apr 11, 2018
Actual Study Completion Date :
May 8, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Atezo-G-Benda (Safety Run-In and Expansion Phases)

Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase.

Drug: Atezolizumab
Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.
Other Names:
  • RO5541267; Tecentriq
  • Drug: Bendamustine
    Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.

    Drug: Obinutuzumab
    Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.
    Other Names:
  • RO5072759
  • Experimental: Atezo-G-CHOP (Safety Run-In Phase)

    Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.

    Drug: Atezolizumab
    Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.
    Other Names:
  • RO5541267; Tecentriq
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Drug: Doxorubicin
    Doxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Drug: Obinutuzumab
    Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.
    Other Names:
  • RO5072759
  • Drug: Prednisone
    Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

    Drug: Vincristine
    Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Experimental: Atezo-R-CHOP (Expansion Phase)

    Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.

    Drug: Atezolizumab
    Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.
    Other Names:
  • RO5541267; Tecentriq
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Drug: Doxorubicin
    Doxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Drug: Prednisone
    Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

    Drug: Vincristine
    Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

    Drug: Rituximab
    Atezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria [Up to approximately 6 months]

      Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.

    2. Percentage of Participants With Adverse Events [Baseline up to approximately 4 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.

    Secondary Outcome Measures

    1. Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria [Up to approximately 6 months]

      Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    2. Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria [Up to approximately 6 months]

      Complete response according to the modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    3. Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria [Up to approximately 6 months]

      Complete response according to modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.

    4. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria [Up to approximately 6 months]

      Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    5. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria [Up to approximately 6 months]

      Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    6. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria [Up to approximately 6 months]

      Tumor response assessment was performed by IRC according to modified Lugano classification using PET/CT scan. OR defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    7. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria [Up to approximately 6 months]

      Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.

    8. Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria [Baseline up to approximately 4 years (assessed at Baseline, 6 to 8 weeks after Day [D] 1 of Cycle [Cy] 6 or 8 (1Cy: 21 or 28 days), then every 2 months up to 24 months, at 35 days of last dose, and at every 3 months post-treatment follow-up [up 4 years])]

      CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.

    9. Observed Serum Obinutuzumab Concentration [Induction: Predose, 0.5 hour (h) postinfusion on Day (D) 1 of Cy1,2,5,6 (1Cy: 21/28 days); Maintenance: Predose, 0.5h postinfusion on Day 1 of Month 1,3,7,15,23; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)]

      Predose time point was "any time prior to dose" for Cycle (Cy) 1 and "within 5 hour prior to dose" for other cycles (Cy 2,5,6) and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 milligrams per hour (mg/hour). If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.

    10. Observed Serum Atezolizumab Concentration [Atezo-R-CHOP: Predose on D1 of Cy2,3,5,8,9,10,11,12,16,20,25 (1Cy:21 days), 0.5h postinfusion of D1 of Cy2,9; at 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)]

      Atezo-G-Benda: Induction:Predose on D1 of Cy5,6 & D1,15 of Cy2,3 (1Cy:21/28 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years); Atezo-G-CHOP: Induction:Predose on D1 of Cy2,3,5,6 (1Cy:21 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,3,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years). Predose time point was "within 5 hour prior to dose" for Cy2,3,5,6 during induction phase and for Months 1 to 24 during maintenance phase. infusion length: 30-60 minutes.

    11. Observed Serum Rituximab Concentration [Predose, 0.5h postinfusion on D1 of Cy1,2,5,8 (1Cy: 21 days); at 120 days and 1 year after last rituximab dose or at treatment discontinuation (up to 4 years)]

      Predose time point was "any time prior to dose" for Cycle 1 and "within 5 hour prior to dose" for other cycles (Cycles 2,5,8) during induction phase and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 mg/hour. If no infusion-related or hypersensitivity reaction occurs, increase the infusion rate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.

    12. Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [Baseline up to approximately 4 years]

      Induction: Predose (any time prior to dose) on D1 of Cy1,5,6 (1Cy: 21/28 days); Maintenance: Predose (any time prior to dose) on D1 of Month 1; at 120 days and 1 year of last obinutuzumab dose or at treatment discontinuation (up to 4 years)

    13. Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab [Baseline up to approximately 4 years]

      Induction: Predose (any time prior to dose) on D1 of Cy1,5,8 (1Cy: 21 days); Maintenance: at 120 days and 1 year of last rituximab dose or at treatment discontinuation (up to 4 years)

    14. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [Baseline up to approximately 4 years]

      Atezo-G-CHOP: Induction: Predose on D1 of Cy2,3,5,6 (1 Cy: 21 days); Maintenance: Predose on D1 of Month 1,2,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years); Atezo-R-CHOP: Predose on D1 of Cy 2,3,5,8,16,25 (1 Cy: 21 days); at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). Predose time point was "any time prior to dose" for Cycles 2,3,5,6,8 during induction phase, for Cycles 16,25 during consolidation treatment, and for Months 1 to 24 during maintenance phase. Atezo-G-Benda: Induction: Predose on D1 of Cy2,3,5,6 (1Cy: 28 days), Cy3D15: Predose; ; Maintenance: Predose on D1 of Month 1,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). The percentage of participants with positive results for ATAs to atezolizumab at baseline and at post-baseline time points are reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

    • For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment

    • For participants enrolled in the expansion phase: lymphoma classified as either previously untreated Grade 1, 2, or 3a FL that requires treatment or previously untreated advanced DLBCL

    • Histologically documented cluster of differentiation 20 (CD20) positive lymphoma

    • Fluorodeoxyglucose-avid lymphoma

    • At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)

    • Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL

    • For women who are not postmenopausal or surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than [<] 1 percent [%] per year during the treatment period and for at least 18 months after the last dose of study treatment for participants in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for participants in the Atezo-R-CHOP treatment group

    • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

    Exclusion Criteria:
    • Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)

    • Central nervous system lymphoma or leptomeningeal infiltration

    • For participants with DLBCL: preplanned consolidative radiotherapy

    • Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1

    • For participants with relapsed or refractory FL: prior allogeneic or autologous stem cell transplantation, anthracycline therapy, treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle 1, treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1, radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1

    • History of solid organ transplantation

    • History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies

    • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab, obinutuzumab, rituximab, or bendamustine formulation, including mannitol

    • Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening

    • History of progressive multifocal leukoencephalopathy

    • Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1

    • History of other malignancy, autoimmune disease, or any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results

    • Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the course of the study

    • For participants who will be receiving CHOP: left ventricular ejection fraction (LVEF) <50% by multiple-gated acquisition (MUGA) scan or echocardiogram

    • Inadequate hematologic, renal, and liver function (unless due to underlying lymphoma)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Rocky Mountain Cancer Center - AuroraAuroraColoradoUnited States80012
    2Georgetown University Medical CenterWashingtonDistrict of ColumbiaUnited States20007
    3University MiamiMiamiFloridaUnited States33136
    4New York Uni Medical CenterNew YorkNew YorkUnited States10016
    5Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065
    6Oncology Associates of Oregon, P.C.; Willamette Valley Cancer InstituteSpringfieldOregonUnited States97477
    7Western Pennsylvania HospitalPittsburghPennsylvaniaUnited States15224
    8Texas OncologyAustinTexasUnited States78705
    9Texas Oncology-TylerIrvingTexasUnited States75063
    10Concord Repatriation General Hospital; HaematologySydneyNew South WalesAustralia2139
    11Calvary Mater NewcastleWaratahNew South WalesAustralia2298
    12The Queen Elizabeth Hospital; Haematology/OncologyWoodville SouthSouth AustraliaAustralia5011
    13Monash Medical CentreClaytonVictoriaAustralia3168
    14Austin HospitalHeidelbergVictoriaAustralia3084
    15Azienda Ospedaliera S. Orsola-MalpighiBolognaEmilia-RomagnaItaly40138
    16Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei TumoriMeldolaEmilia-RomagnaItaly47014
    17Az. Osp. S. Maria Delle Croci; U.O. Di EmatologiaRavennaEmilia-RomagnaItaly48100
    18Ospedale Infermi di RiminiRiminiEmilia-RomagnaItaly47900
    19AOU Città della Salute e della Scienza di Torino - Presidio Le MolinetteTorinoLazioItaly10126
    20Asst Papa Giovanni XXIIIBergamoLombardiaItaly24100
    21Azienda Ospedaliera UnivFirenzeToscanaItaly50141

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02596971
    Other Study ID Numbers:
    • BO29563
    • 2015-001364-19
    First Posted:
    Nov 4, 2015
    Last Update Posted:
    May 24, 2021
    Last Verified:
    Apr 1, 2021

    Study Results

    Participant Flow

    Recruitment DetailsThe study was conducted at 15 sites in 3 countries (Italy, Australia, and USA).
    Pre-assignment DetailOut of the 117 subjects who were screened for this study, 91 subjects were enrolled to either FL treatment cohort (Atezo-G-Benda, Atezo-G-CHOP) or DLBCL cohort (Atezo-R-CHOP) and 26 subjects failed screening.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Period Title: Overall Study
    STARTED42742
    COMPLETED32533
    NOT COMPLETED1029

    Baseline Characteristics

    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)Total
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.Total of all reporting groups
    Overall Participants4274291
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    35
    83.3%
    6
    85.7%
    20
    47.6%
    61
    67%
    >=65 years
    7
    16.7%
    1
    14.3%
    22
    52.4%
    30
    33%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.6
    (10.9)
    57.4
    (5.4)
    59.2
    (15.7)
    57.4
    (13.1)
    Sex: Female, Male (Count of Participants)
    Female
    20
    47.6%
    4
    57.1%
    16
    38.1%
    40
    44%
    Male
    22
    52.4%
    3
    42.9%
    26
    61.9%
    51
    56%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    7.1%
    0
    0%
    2
    4.8%
    5
    5.5%
    Not Hispanic or Latino
    36
    85.7%
    7
    100%
    37
    88.1%
    80
    87.9%
    Unknown or Not Reported
    3
    7.1%
    0
    0%
    3
    7.1%
    6
    6.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    3
    7.1%
    1
    14.3%
    0
    0%
    4
    4.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    37
    88.1%
    6
    85.7%
    40
    95.2%
    83
    91.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    2
    4.8%
    0
    0%
    2
    4.8%
    4
    4.4%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria
    DescriptionPrimary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of relapsed/refractory [r/r] FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    75
    178.6%
    77.5
    1107.1%
    2. Primary Outcome
    TitlePercentage of Participants With Adverse Events
    DescriptionAn 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.
    Time FrameBaseline up to approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants42742
    Number [percentage of participants]
    100
    238.1%
    100
    1428.6%
    100
    238.1%
    3. Secondary Outcome
    TitlePercentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
    DescriptionTumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    87.5
    208.3%
    77.5
    1107.1%
    4. Secondary Outcome
    TitlePercentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
    DescriptionComplete response according to the modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    75.0
    178.6%
    77.5
    1107.1%
    5. Secondary Outcome
    TitlePercentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
    DescriptionComplete response according to modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    80.0
    190.5%
    75.0
    1071.4%
    6. Secondary Outcome
    TitlePercentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
    DescriptionObjective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    90.0
    214.3%
    90.0
    1285.7%
    7. Secondary Outcome
    TitlePercentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
    DescriptionObjective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    95.0
    226.2%
    87.5
    1250%
    8. Secondary Outcome
    TitlePercentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria
    DescriptionTumor response assessment was performed by IRC according to modified Lugano classification using PET/CT scan. OR defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    90.0
    214.3%
    87.5
    1250%
    9. Secondary Outcome
    TitlePercentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
    DescriptionTumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
    Time FrameUp to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy. 2 participants excluded from Atezo-G-Benda cohort (diagnosis of r/r FL). 2 participants excluded in R-Chop-Atezo cohort (they were excluded prior to Cycle 2, were not treated with atezolizumab).
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    95.0
    226.2%
    87.5
    1250%
    10. Secondary Outcome
    TitlePercentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria
    DescriptionCR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.
    Time FrameBaseline up to approximately 4 years (assessed at Baseline, 6 to 8 weeks after Day [D] 1 of Cycle [Cy] 6 or 8 (1Cy: 21 or 28 days), then every 2 months up to 24 months, at 35 days of last dose, and at every 3 months post-treatment follow-up [up 4 years])

    Outcome Measure Data

    Analysis Population Description
    All PET evaluable 1L FL and 1L DLBCL patients that received at least one dose of atezolizumab.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants4040
    Number (90% Confidence Interval) [percentage of participants]
    80.0
    190.5%
    75.0
    1071.4%
    11. Secondary Outcome
    TitleObserved Serum Obinutuzumab Concentration
    DescriptionPredose time point was "any time prior to dose" for Cycle (Cy) 1 and "within 5 hour prior to dose" for other cycles (Cy 2,5,6) and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 milligrams per hour (mg/hour). If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
    Time FrameInduction: Predose, 0.5 hour (h) postinfusion on Day (D) 1 of Cy1,2,5,6 (1Cy: 21/28 days); Maintenance: Predose, 0.5h postinfusion on Day 1 of Month 1,3,7,15,23; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment and who provided at least one pharmacokinetic (PK) sample.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.
    Measure Participants427
    C1 Cmax after 1st infusion
    329
    400
    C1 Cmin after the last infusion on C1
    322
    399
    C6 - Cmax after last dosing of induction
    544
    659
    C6 - Cmin after last dosing of induction
    203
    245
    12. Secondary Outcome
    TitleObserved Serum Atezolizumab Concentration
    DescriptionAtezo-G-Benda: Induction:Predose on D1 of Cy5,6 & D1,15 of Cy2,3 (1Cy:21/28 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years); Atezo-G-CHOP: Induction:Predose on D1 of Cy2,3,5,6 (1Cy:21 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,3,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years). Predose time point was "within 5 hour prior to dose" for Cy2,3,5,6 during induction phase and for Months 1 to 24 during maintenance phase. infusion length: 30-60 minutes.
    Time FrameAtezo-R-CHOP: Predose on D1 of Cy2,3,5,8,9,10,11,12,16,20,25 (1Cy:21 days), 0.5h postinfusion of D1 of Cy2,9; at 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment and who provided at least one pharmacokinetic (PK) sample. 0 represents no data was collected at that cycle.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-R-CHOP Cohort (Expansion Phase)Atezo-G-CHOP Cohort (Safety Run-In Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.
    Measure Participants42427
    Cycle 2 - Cmax after 1st infusion
    275
    332
    424
    C2 - Cmin before 2nd infusion
    83
    82.1
    94
    C6 - Cmin after 6th infusion
    256
    195
    C8 - Cmax after 7th infusion
    486.5
    C8 - Cmin before 8th infusion
    184
    13. Secondary Outcome
    TitleObserved Serum Rituximab Concentration
    DescriptionPredose time point was "any time prior to dose" for Cycle 1 and "within 5 hour prior to dose" for other cycles (Cycles 2,5,8) during induction phase and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 mg/hour. If no infusion-related or hypersensitivity reaction occurs, increase the infusion rate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
    Time FramePredose, 0.5h postinfusion on D1 of Cy1,2,5,8 (1Cy: 21 days); at 120 days and 1 year after last rituximab dose or at treatment discontinuation (up to 4 years)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment and who provided at least one PK sample.
    Arm/Group TitleAtezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionParticipants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants42
    C1 - Cmax after dosing C1
    159
    C1 - Ctrough after dosing C1
    26.1
    C8 - Cmax after dosing C8
    229
    C8 - Ctrough after dosing C8
    105.5
    14. Secondary Outcome
    TitlePercentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
    DescriptionInduction: Predose (any time prior to dose) on D1 of Cy1,5,6 (1Cy: 21/28 days); Maintenance: Predose (any time prior to dose) on D1 of Month 1; at 120 days and 1 year of last obinutuzumab dose or at treatment discontinuation (up to 4 years)
    Time FrameBaseline up to approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    The safety analysis population consisted of all participants who received at least one dose of study drug in the Atezo-G-Benda cohort
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.
    Measure Participants42
    Induction Cycle 1 Day 1
    2.4
    5.7%
    Induction Cycle 5 Day 1
    0
    0%
    Induction Cycle 6 Day 1
    0
    0%
    Maintenance Month 1
    0
    0%
    Study Drug Completion or Early Discontinuation
    0
    0%
    Obinutuzumab Day 120 Follow up
    0
    0%
    15. Secondary Outcome
    TitlePercentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
    DescriptionInduction: Predose (any time prior to dose) on D1 of Cy1,5,8 (1Cy: 21 days); Maintenance: at 120 days and 1 year of last rituximab dose or at treatment discontinuation (up to 4 years)
    Time FrameBaseline up to approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    The safety analysis population consisted of all participants who received at least one dose of study drug in the Atezo-R-CHOP cohort.
    Arm/Group TitleAtezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionParticipants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants42
    Baseline
    14.3
    34%
    Induction Cycle 1 Day 1
    0
    0%
    Induction Cycle 5 Day 1
    0
    0%
    Induction Cycle 8 Day 1
    0
    0%
    Rituximab Day 120 Follow up
    0
    0%
    Rituximab 1 Year Follow up
    0
    0%
    Study Drug Completion or Early Discontinuation
    0
    0%
    16. Secondary Outcome
    TitlePercentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
    DescriptionAtezo-G-CHOP: Induction: Predose on D1 of Cy2,3,5,6 (1 Cy: 21 days); Maintenance: Predose on D1 of Month 1,2,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years); Atezo-R-CHOP: Predose on D1 of Cy 2,3,5,8,16,25 (1 Cy: 21 days); at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). Predose time point was "any time prior to dose" for Cycles 2,3,5,6,8 during induction phase, for Cycles 16,25 during consolidation treatment, and for Months 1 to 24 during maintenance phase. Atezo-G-Benda: Induction: Predose on D1 of Cy2,3,5,6 (1Cy: 28 days), Cy3D15: Predose; ; Maintenance: Predose on D1 of Month 1,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). The percentage of participants with positive results for ATAs to atezolizumab at baseline and at post-baseline time points are reported.
    Time FrameBaseline up to approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study drug.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    Measure Participants42742
    Baseline
    2.4
    5.7%
    0
    0%
    14.3
    34%
    Induction Cycle 2 Day 1
    0
    0%
    0
    0%
    2.6
    6.2%
    Consolidation Cycle 16
    5.9
    14%
    Atezolizumab Day 120 Follow up
    0
    0%
    0
    0%
    9.1
    21.7%
    Atezo PK and Immunogenicity Follow Up (1YR)
    0
    0%
    0
    0%
    5.6
    13.3%

    Adverse Events

    Time FrameBaseline up to approximately 4 years
    Adverse Event Reporting Description The safety population is defined as all patients who received at least one dose of the study medication.
    Arm/Group TitleAtezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Arm/Group DescriptionSafety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL received same treatment regimen as described for safety run-in phase.Safety run-in phase: Participants with previously untreated or relapsed or refractory FL received obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.Participants with previously untreated DLBCL received rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.
    All Cause Mortality
    Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/42 (11.9%) 1/7 (14.3%) 5/42 (11.9%)
    Serious Adverse Events
    Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total19/42 (45.2%) 2/7 (28.6%) 18/42 (42.9%)
    Blood and lymphatic system disorders
    AUTOIMMUNE HAEMOLYTIC ANAEMIA0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    FEBRILE NEUTROPENIA4/42 (9.5%) 41/7 (14.3%) 16/42 (14.3%) 7
    NEUTROPENIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    THROMBOCYTOPENIA0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    Cardiac disorders
    ATRIAL FIBRILLATION0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    ATRIAL TACHYCARDIA1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    CARDIAC ARREST1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    MYOCARDITIS1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Ear and labyrinth disorders
    HYPOACUSIS1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Eye disorders
    DIPLOPIA0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    IMMUNE-MEDIATED ENTEROCOLITIS0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    INTESTINAL OBSTRUCTION0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    NAUSEA1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    PANCREATITIS1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    SMALL INTESTINAL OBSTRUCTION1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    General disorders
    PYREXIA3/42 (7.1%) 30/7 (0%) 00/42 (0%) 0
    SUDDEN DEATH1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Hepatobiliary disorders
    CHOLECYSTITIS0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    Infections and infestations
    DIVERTICULITIS0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    EPSTEIN-BARR VIRUS INFECTION0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    GASTROENTERITIS SALMONELLA0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    KIDNEY INFECTION0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    PNEUMONIA5/42 (11.9%) 50/7 (0%) 02/42 (4.8%) 2
    PNEUMONIA INFLUENZAL0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    PNEUMONIA VIRAL1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY1/42 (2.4%) 10/7 (0%) 01/42 (2.4%) 1
    SEPSIS0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    SINUSITIS0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    SKIN INFECTION1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION2/42 (4.8%) 20/7 (0%) 00/42 (0%) 0
    URINARY TRACT INFECTION1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    URINARY TRACT INFECTION STAPHYLOCOCCAL1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION2/42 (4.8%) 20/7 (0%) 00/42 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    ADENOCARCINOMA OF COLON1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    COLON CANCER1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Nervous system disorders
    MIGRAINE1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    SYNCOPE1/42 (2.4%) 10/7 (0%) 01/42 (2.4%) 1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    LARYNGEAL INFLAMMATION0/42 (0%) 00/7 (0%) 01/42 (2.4%) 1
    OBLITERATIVE BRONCHIOLITIS1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    PULMONARY EMBOLISM1/42 (2.4%) 10/7 (0%) 00/42 (0%) 0
    Other (Not Including Serious) Adverse Events
    Atezo-G-Benda Cohort (Safety Run-In and Expansion Phases)Atezo-G-CHOP Cohort (Safety Run-In Phase)Atezo-R-CHOP Cohort (Expansion Phase)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total42/42 (100%) 7/7 (100%) 42/42 (100%)
    Blood and lymphatic system disorders
    ANAEMIA4/42 (9.5%) 40/7 (0%) 06/42 (14.3%) 8
    IRON DEFICIENCY ANAEMIA0/42 (0%) 01/7 (14.3%) 11/42 (2.4%) 1
    LYMPH NODE PAIN1/42 (2.4%) 11/7 (14.3%) 11/42 (2.4%) 1
    NEUTROPENIA14/42 (33.3%) 223/7 (42.9%) 622/42 (52.4%) 31
    THROMBOCYTOPENIA4/42 (9.5%) 60/7 (0%) 01/42 (2.4%) 1
    Cardiac disorders
    BRADYCARDIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    PALPITATIONS2/42 (4.8%) 22/7 (28.6%) 21/42 (2.4%) 1
    Endocrine disorders
    HYPOPHYSITIS0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    HYPOTHYROIDISM1/42 (2.4%) 11/7 (14.3%) 12/42 (4.8%) 2
    Eye disorders
    DRY EYE2/42 (4.8%) 22/7 (28.6%) 23/42 (7.1%) 3
    OCULAR HYPERAEMIA1/42 (2.4%) 11/7 (14.3%) 10/42 (0%) 0
    PHOTOPHOBIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    VISION BLURRED3/42 (7.1%) 30/7 (0%) 01/42 (2.4%) 1
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT4/42 (9.5%) 40/7 (0%) 00/42 (0%) 0
    ABDOMINAL PAIN8/42 (19%) 102/7 (28.6%) 35/42 (11.9%) 5
    ABDOMINAL PAIN UPPER6/42 (14.3%) 70/7 (0%) 04/42 (9.5%) 4
    ASCITES0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    COLITIS4/42 (9.5%) 40/7 (0%) 00/42 (0%) 0
    CONSTIPATION18/42 (42.9%) 273/7 (42.9%) 418/42 (42.9%) 26
    DEFAECATION URGENCY0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    DIARRHOEA20/42 (47.6%) 473/7 (42.9%) 1014/42 (33.3%) 23
    DRY MOUTH5/42 (11.9%) 50/7 (0%) 04/42 (9.5%) 4
    DUODENAL ULCER HAEMORRHAGE0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    DYSPEPSIA8/42 (19%) 111/7 (14.3%) 12/42 (4.8%) 3
    FLATULENCE3/42 (7.1%) 40/7 (0%) 00/42 (0%) 0
    GASTROOESOPHAGEAL REFLUX DISEASE3/42 (7.1%) 31/7 (14.3%) 10/42 (0%) 0
    GLOSSITIS1/42 (2.4%) 11/7 (14.3%) 10/42 (0%) 0
    HAEMATOCHEZIA1/42 (2.4%) 11/7 (14.3%) 10/42 (0%) 0
    HAEMORRHOIDAL HAEMORRHAGE0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    NAUSEA22/42 (52.4%) 425/7 (71.4%) 813/42 (31%) 22
    RECTAL DISCHARGE0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    STEATORRHOEA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    STOMATITIS3/42 (7.1%) 30/7 (0%) 03/42 (7.1%) 5
    VOMITING11/42 (26.2%) 152/7 (28.6%) 39/42 (21.4%) 11
    General disorders
    ASTHENIA3/42 (7.1%) 50/7 (0%) 02/42 (4.8%) 4
    CHEST DISCOMFORT2/42 (4.8%) 21/7 (14.3%) 12/42 (4.8%) 2
    CHEST PAIN10/42 (23.8%) 101/7 (14.3%) 14/42 (9.5%) 4
    CHILLS3/42 (7.1%) 50/7 (0%) 01/42 (2.4%) 1
    FATIGUE23/42 (54.8%) 275/7 (71.4%) 617/42 (40.5%) 22
    FEELING COLD0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    INFLUENZA LIKE ILLNESS7/42 (16.7%) 91/7 (14.3%) 11/42 (2.4%) 1
    MUCOSAL INFLAMMATION1/42 (2.4%) 22/7 (28.6%) 33/42 (7.1%) 5
    OEDEMA PERIPHERAL3/42 (7.1%) 31/7 (14.3%) 13/42 (7.1%) 4
    PAIN2/42 (4.8%) 21/7 (14.3%) 10/42 (0%) 0
    PERIPHERAL SWELLING3/42 (7.1%) 31/7 (14.3%) 21/42 (2.4%) 1
    PYREXIA10/42 (23.8%) 120/7 (0%) 05/42 (11.9%) 9
    Hepatobiliary disorders
    CHOLELITHIASIS0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Immune system disorders
    SEASONAL ALLERGY3/42 (7.1%) 50/7 (0%) 02/42 (4.8%) 2
    Infections and infestations
    BRONCHITIS4/42 (9.5%) 41/7 (14.3%) 20/42 (0%) 0
    CONJUNCTIVITIS2/42 (4.8%) 22/7 (28.6%) 20/42 (0%) 0
    HERPES ZOSTER2/42 (4.8%) 22/7 (28.6%) 21/42 (2.4%) 1
    NASOPHARYNGITIS5/42 (11.9%) 80/7 (0%) 01/42 (2.4%) 1
    ORAL CANDIDIASIS2/42 (4.8%) 21/7 (14.3%) 20/42 (0%) 0
    ORAL HERPES0/42 (0%) 01/7 (14.3%) 11/42 (2.4%) 1
    PHARYNGITIS STREPTOCOCCAL0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    PNEUMONIA4/42 (9.5%) 40/7 (0%) 02/42 (4.8%) 2
    SINUSITIS7/42 (16.7%) 71/7 (14.3%) 15/42 (11.9%) 5
    SKIN INFECTION2/42 (4.8%) 21/7 (14.3%) 11/42 (2.4%) 1
    UPPER RESPIRATORY TRACT INFECTION12/42 (28.6%) 221/7 (14.3%) 17/42 (16.7%) 7
    URINARY TRACT INFECTION6/42 (14.3%) 81/7 (14.3%) 11/42 (2.4%) 2
    VULVOVAGINAL MYCOTIC INFECTION1/42 (2.4%) 11/7 (14.3%) 10/42 (0%) 0
    Injury, poisoning and procedural complications
    FALL1/42 (2.4%) 11/7 (14.3%) 13/42 (7.1%) 5
    INFUSION RELATED REACTION29/42 (69%) 452/7 (28.6%) 216/42 (38.1%) 16
    JOINT DISLOCATION0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    LIGAMENT SPRAIN0/42 (0%) 01/7 (14.3%) 20/42 (0%) 0
    MENISCUS INJURY0/42 (0%) 02/7 (28.6%) 20/42 (0%) 0
    POST PROCEDURAL HAEMATURIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    PROCEDURAL PAIN2/42 (4.8%) 31/7 (14.3%) 10/42 (0%) 0
    SKIN LACERATION2/42 (4.8%) 21/7 (14.3%) 10/42 (0%) 0
    Investigations
    AMYLASE INCREASED4/42 (9.5%) 40/7 (0%) 03/42 (7.1%) 3
    LIPASE INCREASED13/42 (31%) 141/7 (14.3%) 14/42 (9.5%) 6
    WEIGHT DECREASED1/42 (2.4%) 10/7 (0%) 03/42 (7.1%) 3
    Metabolism and nutrition disorders
    DECREASED APPETITE6/42 (14.3%) 62/7 (28.6%) 21/42 (2.4%) 1
    DEHYDRATION2/42 (4.8%) 32/7 (28.6%) 22/42 (4.8%) 2
    HYPERGLYCAEMIA3/42 (7.1%) 30/7 (0%) 00/42 (0%) 0
    HYPOCALCAEMIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    HYPOKALAEMIA1/42 (2.4%) 10/7 (0%) 03/42 (7.1%) 3
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA8/42 (19%) 102/7 (28.6%) 49/42 (21.4%) 12
    BACK PAIN10/42 (23.8%) 104/7 (57.1%) 68/42 (19%) 13
    BONE PAIN4/42 (9.5%) 61/7 (14.3%) 14/42 (9.5%) 5
    FLANK PAIN3/42 (7.1%) 60/7 (0%) 02/42 (4.8%) 2
    JOINT EFFUSION0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    JOINT SWELLING0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    MUSCLE SPASMS5/42 (11.9%) 72/7 (28.6%) 20/42 (0%) 0
    MUSCULOSKELETAL CHEST PAIN2/42 (4.8%) 51/7 (14.3%) 14/42 (9.5%) 4
    MUSCULOSKELETAL PAIN4/42 (9.5%) 41/7 (14.3%) 12/42 (4.8%) 2
    MUSCULOSKELETAL STIFFNESS1/42 (2.4%) 11/7 (14.3%) 10/42 (0%) 0
    MYALGIA2/42 (4.8%) 31/7 (14.3%) 15/42 (11.9%) 5
    NECK PAIN4/42 (9.5%) 40/7 (0%) 02/42 (4.8%) 2
    PAIN IN EXTREMITY8/42 (19%) 101/7 (14.3%) 12/42 (4.8%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACROCHORDON0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    NEOPLASM0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    OVARIAN EPITHELIAL CANCER0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Nervous system disorders
    AMNESIA1/42 (2.4%) 11/7 (14.3%) 11/42 (2.4%) 2
    BALANCE DISORDER0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    DIZZINESS7/42 (16.7%) 121/7 (14.3%) 14/42 (9.5%) 6
    DYSGEUSIA0/42 (0%) 00/7 (0%) 06/42 (14.3%) 6
    HEADACHE19/42 (45.2%) 251/7 (14.3%) 18/42 (19%) 13
    HYPOAESTHESIA4/42 (9.5%) 42/7 (28.6%) 31/42 (2.4%) 1
    PARAESTHESIA3/42 (7.1%) 50/7 (0%) 03/42 (7.1%) 3
    PERIPHERAL SENSORY NEUROPATHY3/42 (7.1%) 32/7 (28.6%) 313/42 (31%) 15
    TASTE DISORDER2/42 (4.8%) 20/7 (0%) 03/42 (7.1%) 3
    Product Issues
    DEVICE OCCLUSION0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Psychiatric disorders
    ANXIETY7/42 (16.7%) 70/7 (0%) 03/42 (7.1%) 6
    INSOMNIA7/42 (16.7%) 72/7 (28.6%) 27/42 (16.7%) 8
    MANIA0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Renal and urinary disorders
    DYSURIA1/42 (2.4%) 31/7 (14.3%) 11/42 (2.4%) 1
    MICTURITION URGENCY0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Reproductive system and breast disorders
    VAGINAL DISCHARGE2/42 (4.8%) 21/7 (14.3%) 10/42 (0%) 0
    VAGINAL HAEMORRHAGE0/42 (0%) 01/7 (14.3%) 20/42 (0%) 0
    VULVOVAGINAL PAIN3/42 (7.1%) 30/7 (0%) 00/42 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    COUGH25/42 (59.5%) 315/7 (71.4%) 912/42 (28.6%) 18
    DYSPHONIA3/42 (7.1%) 30/7 (0%) 02/42 (4.8%) 2
    DYSPNOEA7/42 (16.7%) 81/7 (14.3%) 13/42 (7.1%) 4
    EPISTAXIS3/42 (7.1%) 30/7 (0%) 02/42 (4.8%) 2
    HICCUPS0/42 (0%) 00/7 (0%) 03/42 (7.1%) 3
    NASAL CONGESTION8/42 (19%) 80/7 (0%) 03/42 (7.1%) 3
    OROPHARYNGEAL PAIN8/42 (19%) 111/7 (14.3%) 14/42 (9.5%) 4
    PHARYNGEAL DISORDER0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    PRODUCTIVE COUGH4/42 (9.5%) 41/7 (14.3%) 10/42 (0%) 0
    RHINITIS ALLERGIC3/42 (7.1%) 31/7 (14.3%) 13/42 (7.1%) 3
    RHINORRHOEA3/42 (7.1%) 32/7 (28.6%) 25/42 (11.9%) 6
    SINUS CONGESTION1/42 (2.4%) 11/7 (14.3%) 12/42 (4.8%) 2
    UPPER-AIRWAY COUGH SYNDROME1/42 (2.4%) 10/7 (0%) 03/42 (7.1%) 4
    Skin and subcutaneous tissue disorders
    ALOPECIA3/42 (7.1%) 42/7 (28.6%) 210/42 (23.8%) 10
    DERMATITIS ACNEIFORM1/42 (2.4%) 11/7 (14.3%) 12/42 (4.8%) 2
    DERMATITIS CONTACT0/42 (0%) 01/7 (14.3%) 20/42 (0%) 0
    DRY SKIN4/42 (9.5%) 41/7 (14.3%) 11/42 (2.4%) 1
    ERYTHEMA4/42 (9.5%) 50/7 (0%) 00/42 (0%) 0
    NIGHT SWEATS4/42 (9.5%) 40/7 (0%) 03/42 (7.1%) 3
    PRURITUS12/42 (28.6%) 140/7 (0%) 04/42 (9.5%) 4
    RASH14/42 (33.3%) 220/7 (0%) 04/42 (9.5%) 6
    RASH MACULO-PAPULAR4/42 (9.5%) 50/7 (0%) 00/42 (0%) 0
    RASH VESICULAR0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0
    Vascular disorders
    HYPERTENSION6/42 (14.3%) 90/7 (0%) 01/42 (2.4%) 1
    PERIPHERAL COLDNESS0/42 (0%) 01/7 (14.3%) 10/42 (0%) 0

    Limitations/Caveats

    Development of the atezolizumab combination treatment was discontinued as there was insufficient evidence regarding the additive efficacy of this therapy.

    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/TitleMedical Communications
    OrganizationHoffmann-La Roche
    Phone800 821-8590
    Emailgenentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02596971
    Other Study ID Numbers:
    • BO29563
    • 2015-001364-19
    First Posted:
    Nov 4, 2015
    Last Update Posted:
    May 24, 2021
    Last Verified:
    Apr 1, 2021