A Phase Ib Study of The Safety and Pharmacology of Atezolizumab in Combination With an Immunotherapy Agent Investigated With or Without Anti-Cd20 Therapy in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Lymphoma, Non-Hodgkin
- Sponsor
- Hoffmann-La Roche
- Locations
- 2
- Primary Endpoint
- Percentage of Participants with Adverse Events
- Status
- Withdrawn
- Last Updated
- 8 years ago
Overview
Brief Summary
This study will investigate the safety, pharmacology, and activity of atezolizumab in combination with immunotherapy agents with or without an anti-CD20 agent (i.e., obinutuzumab) in patients with relapsed or refractory (R/R) follicular lymphoma (FL). The first immunotherapy molecule investigated will be emactuzumab (Arm A) in two combinations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- •Life expectancy ≥ 12 weeks
- •At least two bi-dimensionally measurable nodal lesions ≥ 1.5 centimeters (cm) in its longest diameter by imaging
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent
- •For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
- •Consent to collection of a pre-treatment tumor sample, on-treatment biopsy, and, if applicable, a tumor tissue sample at the time of progressive disease (PD)
- •Inclusion Criteria Specific to Obinutuzumab-Containing Cohorts
- •Patients receiving therapeutic anticoagulation should be switched to low molecular weight heparin (LMWH) before the first cycle of obinutuzumab
Exclusion Criteria
- •Any approved systemic anti-cancer therapy (including chemotherapy) or hormonal therapy within 3 weeks prior to initiation of study treatment
- •Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
- •Known central nervous system (CNS) lymphoma, leptomeningeal lymphoma
- •Grade 3b FL, small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), or other lymphoma subtypes except as stated in the inclusion criteria
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled hypercalcemia
- •History of other malignancy within 5 years prior to screening with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
- •Known hypersensitivity to any of the study drugs
- •History of sensitivity to mannitol
Arms & Interventions
Atezolizumab + Emactuzumab
Participants will receive Atezolizumab and Emactuzumab on Day 1 of each 21- day cycle
Intervention: Atezolizumab
Atezolizumab + Emactuzumab
Participants will receive Atezolizumab and Emactuzumab on Day 1 of each 21- day cycle
Intervention: Emactuzumab
Atezolizumab + Emactuzumab + Obinutuzumab
Participants will receive Atezolizumab, Emactuzumab, and Obinutuzumab on Day 1 of each- 21 day cycle (starting in cycle 2) (Atezolizumab starting in cycle 2); and Obinutuzumab on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-8.
Intervention: Atezolizumab
Atezolizumab + Emactuzumab + Obinutuzumab
Participants will receive Atezolizumab, Emactuzumab, and Obinutuzumab on Day 1 of each- 21 day cycle (starting in cycle 2) (Atezolizumab starting in cycle 2); and Obinutuzumab on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-8.
Intervention: Emactuzumab
Atezolizumab + Emactuzumab + Obinutuzumab
Participants will receive Atezolizumab, Emactuzumab, and Obinutuzumab on Day 1 of each- 21 day cycle (starting in cycle 2) (Atezolizumab starting in cycle 2); and Obinutuzumab on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-8.
Intervention: Obinutuzumab
Outcomes
Primary Outcomes
Percentage of Participants with Adverse Events
Time Frame: Baseline to end of study (approximately 48 months)
Secondary Outcomes
- Duration of Objective Response (DOR)(Baseline to end of study (approximately 48 months))
- Serum concentration of Atezolizumab at specified timepoints(Cohort A1 and A3 Cycle 2-4, Day 1 pre and post infusion; Cycle 6, 8, Day 1 pre-infusion; Every 8 cycles after cycle 8, Day 1 pre-infusion. Cohort A2 and A4 Cycle 2 and 4, Day 1 pre- and post infusion, Cycle 3,6, and 8, Day 1 pre-infusion.)
- Objective Response(Baseline to end of study (approximately 48 months))
- Serum concentration of Obinutuzumab at specified timepoints(Cohort A2 and A4 Cycle 1,6,8, and every 8 cycles post cycle 8, Day 1 prior to infusion; Cycle 1, Day 2, post infusion; Cycle 1, Day 8 and 15, pre and post infusion; Cycle 2,3, and 4, Day 1, pre and post infusion. (Cycle = 21 days))
- Overall Survival (OS)(Baseline to end of study (approximately 48 months))
- Serum concentration of Emactuzumab at specified timepoints(Cohort A1 and A3 Cycle 1-4, Day 1 pre and post infusion; Cycle 6, 8 and every 8 cycles post cycle 8, pre-infusion. Cycle 1-4 Day 1 pre and post infusion; Cycle 1, Day 15 pre-infusion. Cycle 6, 8 and every 8 cycles post cycle 8, Day 1 pre-infusion.)
- Progression Free Survival (PFS)(Baseline to end of study (approximately 48 months))