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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-Hodgkin Lymphoma, Follicular Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab SC; Drug: Tiragolumab; Other: Tocilizumab; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
  • Victoria
    • Box Hill, Victoria, Australia
      • Eastern Health
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan Brugge Oostende AV
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Yvoir, Belgium, 5530
    • CHU UCL Namur - Mont-Godinne
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre-Calgary
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre
• Germany
  • Essen, Germany, 45122
    • Universitaet Duisburg-Essen
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West Of Scotland Cancer Centre
  • London, United Kingdom, SE3 6JJ
    • Royal Marsden Hospital - Institute of Cancer Research - Chelsea
  • Plymouth, United Kingdom
    • Plymouth Hospitals NHS Trust - Derriford Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital - Institute of Cancer Research - Sutton
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Lifespan Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Best ORR as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b	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.	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)
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): July 19, 2023
• Study Completion (Actual): July 19, 2023

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: B-Cell Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: CO43116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No