An Open-Label, Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab in Combination With Tiragolumab With or Without Atezolizumab in Participants With B-Cell Non-Hodgkin Lymphoma
Phase 1
Terminated
- Conditions
- Non-Hodgkin Lymphoma, Follicular Lymphoma
- Interventions
- Registration Number
- NCT05315713
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab in combination with tiragolumab, with or without atezolizumab, in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) who have received at least two previous lines of systemic therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
Inclusion Criteria
- Aged >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- Histologically documented FL or DLBCL that has relapsed or failed to respond to at least two prior systemic treatment regimens and for which no suitable therapy of curative intent or higher priority exists (e.g., standard chemotherapy, ASCT, CAR T cells)
- At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or at least one bi-dimensionally measurable (> 1.0 cm) extranodal lesion
- Participants with FL (including trFL) for whom a bone marrow biopsy and aspirate can be collected
- Adequate hematologic and organ function
Exclusion Criteria
- Received any of the following treatments prior to study entry: mosunetuzumab or other CD20/CD3-directed bispecific antibodies; tiragolumab or other anti-TIGIT agent; allogenic SCT; solid organ transplantation
- Currently eligible for autologous SCT
- Current or past history of CNS lymphoma or leptomeningeal infiltration
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- Contraindication to atezolizumab (if applicable) or tocilizumab
- Clinically significant toxicities from prior treatment have not resolved to Grade </= 1 (per NCI CTCAE v5.0) prior to the first study drug administration with exceptions defined by the protocol
- Treatment-emergent immune-mediated adverse events associated with prior immunotherapeutic agents as defined by the protocol
- Evidence of any significant, concomitant disease as defined by the protocol
- Major surgery within 4 weeks prior to first study treatment administration, with the exception of protocol-mandated procedures (e.g., tumor biopsies and bone marrow biopsies)
- Significant cardiac, pulmonary, CNS, or liver disease, or known active infections
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- History of autoimmune disease with exceptions as defined in the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab Mosunetuzumab SC Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab Tocilizumab Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV Mosunetuzumab SC Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Note: This arm did not enroll any participants. Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV Tocilizumab Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Note: This arm did not enroll any participants. Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab Tiragolumab Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV Tiragolumab Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Note: This arm did not enroll any participants. Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV Atezolizumab Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) Note: This arm did not enroll any participants.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events - Phase 1b From the start of treatment until 90 days after the final dose of study treatment (up to 36 weeks) Best Objective Response Rate (ORR) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2 Up to Cycle 17 (cycle length = 21 days)
- Secondary Outcome Measures
Name Time Method Best ORR as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b Assessed at screening and then every 3-6 months until disease progression, start of new anti-cancer therapy, or withdrawal (through Cycle 8; cycle length = 21 days) Best ORR is defined as the fraction of participants with complete response (CR) or partial response (PR) at any time as determined by the investigator using Lugano 2014 criteria.
Serum Concentration of Mosunetuzumab - Phase 1b Cycle 1 Day 1 - Cycle 8 Day 1 (cycle length = 21 days) Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b Assessed at screening and then every 3-6 months until disease progression, start of new anti-cancer therapy, or withdrawal (through Cycle 8; cycle length = 21 days) Duration of Response (DOR) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b and Phase 2 From the first occurrence of a documented response (CR or partial response (PR)) to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 4 years) Progression-Free Survival (PFS) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2 From the first study treatment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 4 years) Event-Free Survival (EFS) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2 From the first study treatment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 4 years) Overall Survival (OS) - Phase 2 From the time of first study treatment to death from any cause (up to approximately 4 years) Percentage of Participants With Adverse Events - Phase 2 From the start of treatment until 90 days after the final dose of study treatment
Trial Locations
- Locations (17)
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
CHU UCL Namur - Mont-Godinne
🇧🇪Yvoir, Belgium
Universitaet Duisburg-Essen
🇩🇪Essen, Germany
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Eastern Health
🇦🇺Box Hill, Victoria, Australia
Tom Baker Cancer Centre-Calgary
🇨🇦Calgary, Alberta, Canada
AZ Sint Jan Brugge Oostende AV
🇧🇪Brugge, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Royal Marsden Hospital - Institute of Cancer Research - Sutton
🇬🇧Sutton, United Kingdom
Plymouth Hospitals NHS Trust - Derriford Hospital
🇬🇧Plymouth, United Kingdom
Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Royal Marsden Hospital - Institute of Cancer Research - Chelsea
🇬🇧London, United Kingdom