Phase 2
Completed N=91
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)
Source: ClinicalTrials.gov NCT02596971 ↗Enrolled (actual)
91
Serious AEs
42.9%
Results posted
Jun 2019
Primary outcomePrimary: 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 — 75; 77.5 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
75; 77.5 | — |
| PRIMARY Percentage of Participants With Adverse Events |
100; 100; 100 | — |
| SECONDARY Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria |
87.5; 77.5 | — |
| SECONDARY Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria |
75.0; 77.5 | — |
| SECONDARY Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria |
80.0; 75.0 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria |
90.0; 90.0 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria |
95.0; 87.5 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria |
90.0; 87.5 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria |
95.0; 87.5 | — |
| SECONDARY Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria |
80.0; 75.0 | — |
| SECONDARY Observed Serum Obinutuzumab Concentration |
329; 400; 322; 399; 544; 659 | — |
| SECONDARY Observed Serum Atezolizumab Concentration |
275; 332; 424; 83; 82.1; 94 | — |
| SECONDARY Observed Serum Rituximab Concentration |
159; 26.1; 229; 105.5 | — |
| SECONDARY Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab |
2.4; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab |
14.3; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab |
2.4; 0; 14.3; 0; 0; 2.6 | — |
Eligibility Criteria
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)
Data sourced from ClinicalTrials.gov (NCT02596971). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.