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)

Browse trials for

• Lymphoma 5,579
• Lymphoma, Follicular 931
• Lymphoma, B-Cell 1,410
• Lymphoma, Large B-Cell, Diffuse 1,389

Lymphoma

5,579 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 91 is above the median of 40 across 4,509 interventional studies indexed under Lymphoma.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• 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 · Drug: Bendamustine · Drug: Obinutuzumab

• 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 · Drug: Cyclophosphamide · Drug: Doxorubicin · Drug: Obinutuzumab · Drug: Prednisone · Drug: Vincristine

• 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 · Drug: Cyclophosphamide · Drug: Doxorubicin · Drug: Prednisone · Drug: Vincristine · Drug: Rituximab

Interventions

• DrugAtezolizumab

  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.

  Also known as: RO5541267; Tecentriq

• DrugBendamustine

  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.

• DrugCyclophosphamide

  Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

• DrugDoxorubicin

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

• DrugObinutuzumab

  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.

  Also known as: RO5072759

• DrugPrednisone

  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).

• DrugVincristine

  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.

• DrugRituximab

  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.

Primary outcomes

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

   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.

   Time frame: Up to approximately 6 months

2. Percentage of Participants With Adverse Events

   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.

   Time frame: Baseline up to approximately 4 years

Secondary outcomes

1. Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria

   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.

   Time frame: Up to approximately 6 months

2. Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria

   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.

   Time frame: Up to approximately 6 months

3. Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria

   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.

   Time frame: Up to approximately 6 months

4. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria

   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.

   Time frame: Up to approximately 6 months

5. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria

   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.

   Time frame: Up to approximately 6 months

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

   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.

   Time frame: Up to approximately 6 months

7. Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria

   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.

   Time frame: Up to approximately 6 months

8. Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria

   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.

   Time frame: 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])

9. Observed Serum Obinutuzumab Concentration

   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.

   Time frame: 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)

10. Observed Serum Atezolizumab Concentration

    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.

    Time frame: 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)

11. Observed Serum Rituximab Concentration

    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.

    Time frame: 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)

12. Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab

    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)

    Time frame: Baseline up to approximately 4 years

13. Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab

    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)

    Time frame: Baseline up to approximately 4 years

14. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

    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.

    Time frame: Baseline up to approximately 4 years

Baseline characteristics

Publications

• Younes A, Burke JM, Diefenbach C, Ferrari S, Khan C, Sharman JP, Tani M, Ujjani C, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Gilbertson M. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022 Oct 25;6(20):5659-5667. doi: 10.1182/bloodadvances.2021006131. PubMed 35359000 ↗

Study documents

• Protocol and statistical analysis plan · Nov 7, 2018

Documents are hosted by the registry — open the source record to download them.