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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib/II Open-Label, Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab in Combination With Tiragolumab With or Without Atezolizumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Conditions
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Non-Hodgkin Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Drug: Mosunetuzumab SC
* Drug: Tiragolumab
* Drug: Atezolizumab
* Other: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab<br>Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) | Drug: Mosunetuzumab SC<br>* Participants will receive SC mosunetuzumab for up to 17 treatment cycles (cycle length = 21 days)<br>Drug: Tiragolumab<br>* Participants will receive IV tiragolumab every 3 weeks (Q3W) for up to 17 treatment cycles (cycle length = 21 days)<br>Other: Tocilizumab<br>* Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events<br>|
| Experimental: Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV<br>Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days) | Drug: Mosunetuzumab SC<br>* Participants will receive SC mosunetuzumab for up to 17 treatment cycles (cycle length = 21 days)<br>Drug: Tiragolumab<br>* Participants will receive IV tiragolumab every 3 weeks (Q3W) for up to 17 treatment cycles (cycle length = 21 days)<br>Drug: Atezolizumab<br>* Participants will receive IV atezolizumab Q3W for up to 17 treatment cycles (cycle length = 21 days)<br>Other: Tocilizumab<br>* Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (Phase 1b) |  | Up to 90 days after the final dose of study treatment (up to Cycle 17; cycle length = 21 days) | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best ORR as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b) |  | Baseline up to approximately 4 years (assessed at screening, and then ever 3-6 months until disease progression, start of new anti-cancer therapy, or withdrawal) | 
| Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b and Phase 2) |  | Baseline up to approximately 4 years (assessed at screening, and then ever 3-6 months until disease progression, start of new anti-cancer therapy, or withdrawal) | 
| 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) |  | Up to 90 days after the final dose of study treatment (up to Cycle 17; cycle length = 21 days) | 
| Serum Concentration of Mosunetuzumab |  | Up to Cycle 17 (cycle length = 21 days) | 
| Serum Concentration of Mosunetuzumab in Combination with Tiragolumab |  | Up to Cycle 17 (cycle length = 17 days) | 
| Serum Concentration of Mosunetuzumab in Combination with Tiragolumab and Atezolizumab |  | Up to Cycle 17 (cycle length = 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-Cell Non-Hodgkin Lymphoma