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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 21
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Bendamustine (Drug)
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.
干预措施: Obinutuzumab (Drug)
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Doxorubicin (Drug)
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.
干预措施: Obinutuzumab (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Vincristine (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Doxorubicin (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Vincristine (Drug)
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.
干预措施: Rituximab (Drug)
结局指标
主要结局
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
时间窗: 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.
Percentage of Participants With Adverse Events
时间窗: 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.
次要结局
- Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria(Up to approximately 6 months)
- Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria(Up to approximately 6 months)
- 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)
- Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria(Up to approximately 6 months)
- 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)
- 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)
- 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)
- 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))
- Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab(Baseline up to approximately 4 years)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab(Baseline up to approximately 4 years)
- 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]))
- 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))
- 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))
- Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab(Baseline up to approximately 4 years)