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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05315713

Collaborator

(none)

118

Enrollment

Locations

Arms

40.2

Anticipated Duration (Months)

7.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma, Follicular Lymphoma	Drug: Mosunetuzumab SC Drug: Tiragolumab Drug: Atezolizumab Other: Tocilizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

118 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2022

Anticipated Primary Completion Date :

Sep 14, 2025

Anticipated Study Completion Date :

Sep 14, 2025

Arms and Interventions

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)	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) Drug: Atezolizumab Participants will receive IV atezolizumab 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

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)

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)

Drug: Atezolizumab

Participants will receive IV atezolizumab 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

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109-0934
2	Lifespan Cancer Institute	Providence	Rhode Island	United States	02905
3	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
4	Eastern Health	Box Hill	Victoria	Australia
5	St Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia	3065
6	AZ Sint Jan Brugge Oostende AV	Brugge		Belgium	8000
7	Institut Jules Bordet	Bruxelles		Belgium	1000
8	AZ Groeninge	Kortrijk		Belgium	8500
9	CHU UCL Namur - Mont-Godinne	Yvoir		Belgium	5530
10	Tom Baker Cancer Centre-Calgary	Calgary	Alberta	Canada	T2N 4N2
11	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 1Z5
12	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
13	Royal Marsden Hospital - Institute of Cancer Research - Chelsea	London		United Kingdom	SE3 6JJ
14	Plymouth Hospitals NHS Trust - Derriford Hospital	Plymouth		United Kingdom
15	Royal Marsden Hospital - Institute of Cancer Research - Sutton	Sutton		United Kingdom	SM2 5PT