Back to results

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

Primary Purpose

Non-Hodgkin Lymphoma, Follicular Lymphoma

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Mosunetuzumab SC

Tiragolumab

Atezolizumab

Tocilizumab

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma, Follicular Lymphoma focused on measuring B-Cell Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

USC Norris Comprehensive Cancer Center
University of Michigan
Lifespan Cancer Institute
St Vincent's Hospital Sydney
Eastern Health
St Vincent's Hospital Melbourne
AZ Sint Jan Brugge Oostende AV
Institut Jules Bordet
AZ Groeninge
CHU UCL Namur - Mont-Godinne
Tom Baker Cancer Centre-Calgary
Princess Margaret Cancer Centre
Universitaet Duisburg-Essen
Beatson West of Scotland Cancer Centre
Royal Marsden Hospital - Institute of Cancer Research - Chelsea
Plymouth Hospitals NHS Trust - Derriford Hospital
Royal Marsden Hospital - Institute of Cancer Research - Sutton

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab

Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV

Arm Description

Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days)

Outcomes

Primary Outcome Measures

Percentage of Participants with Adverse Events (Phase 1b)

Best Objective Response Rate (ORR) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Secondary Outcome Measures

Best ORR as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b)

Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b and Phase 2)

Duration of Response (DOR) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b and Phase 2)

Progression-Free Survival (PFS) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Event-Free Survival (EFS) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Overall Survival (OS) (Phase 2)

Percentage of Participants with Adverse Events (Phase 2)

Serum Concentration of Mosunetuzumab

Serum Concentration of Mosunetuzumab in Combination with Tiragolumab

Serum Concentration of Mosunetuzumab in Combination with Tiragolumab and Atezolizumab

Full Information

NCT ID

NCT05315713

First Posted

March 31, 2022

Last Updated

October 18, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT05315713

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 10, 2022 (Actual)

Primary Completion Date

December 15, 2023 (Anticipated)

Study Completion Date

December 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Hodgkin Lymphoma, Follicular Lymphoma

Keywords

B-Cell Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

118 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Subcutaneous (SC) Mosunetuzumab in Combination with Intravenous (IV) Tiragolumab

Arm Type

Experimental

Arm Description

Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days)

Arm Title

Mosunetuzumab SC in Combination with Tiragolumab IV and Atezolizumab IV

Arm Type

Experimental

Arm Description

Participants will receive at least 8 and up to 17 cycles of treatment (cycle length = 21 days)

Intervention Type

Drug

Intervention Name(s)

Mosunetuzumab SC

Intervention Description

Participants will receive SC mosunetuzumab for up to 17 treatment cycles (cycle length = 21 days)

Intervention Type

Drug

Intervention Name(s)

Tiragolumab

Intervention Description

Participants will receive IV tiragolumab every 3 weeks (Q3W) for up to 17 treatment cycles (cycle length = 21 days)

Intervention Type

Drug

Intervention Name(s)

Atezolizumab

Intervention Description

Participants will receive IV atezolizumab Q3W for up to 17 treatment cycles (cycle length = 21 days)

Intervention Type

Other

Intervention Name(s)

Tocilizumab

Intervention Description

Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

Primary Outcome Measure Information:

Title

Percentage of Participants with Adverse Events (Phase 1b)

Time Frame

Up to 90 days after the final dose of study treatment (up to Cycle 17; cycle length = 21 days)

Title

Best Objective Response Rate (ORR) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Time Frame

Up to Cycle 17 (cycle length = 21 days)

Secondary Outcome Measure Information:

Title

Best ORR as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b)

Time Frame

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)

Title

Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b and Phase 2)

Time Frame

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)

Title

Duration of Response (DOR) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 1b and Phase 2)

Time Frame

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)

Title

Progression-Free Survival (PFS) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Time Frame

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)

Title

Event-Free Survival (EFS) as Determined by the Investigator Using Lugano 2014 Criteria (Phase 2)

Time Frame

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)

Title

Overall Survival (OS) (Phase 2)

Time Frame

From the time of first study treatment to death from any cause (up to approximately 4 years)

Title

Percentage of Participants with Adverse Events (Phase 2)

Time Frame

Up to 90 days after the final dose of study treatment (up to Cycle 17; cycle length = 21 days)

Title

Serum Concentration of Mosunetuzumab

Time Frame

Up to Cycle 17 (cycle length = 21 days)

Title

Serum Concentration of Mosunetuzumab in Combination with Tiragolumab

Time Frame

Up to Cycle 17 (cycle length = 17 days)

Title

Serum Concentration of Mosunetuzumab in Combination with Tiragolumab and Atezolizumab

Time Frame

Up to Cycle 17 (cycle length = 21 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

USC Norris Comprehensive Cancer Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109-0934

Country

United States

Facility Name

Lifespan Cancer Institute

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02905

Country

United States

Facility Name

St Vincent's Hospital Sydney

City

Darlinghurst

State/Province

New South Wales

ZIP/Postal Code

2010

Country

Australia

Facility Name

Eastern Health

City

Box Hill

State/Province

Victoria

Country

Australia

Facility Name

St Vincent's Hospital Melbourne

City

Fitzroy

State/Province

Victoria

ZIP/Postal Code

3065

Country

Australia

Facility Name

AZ Sint Jan Brugge Oostende AV

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Institut Jules Bordet

City

Bruxelles

ZIP/Postal Code

1000

Country

Belgium

Facility Name

AZ Groeninge

City

Kortrijk

ZIP/Postal Code

8500

Country

Belgium

Facility Name

CHU UCL Namur - Mont-Godinne

City

Yvoir

ZIP/Postal Code

5530

Country

Belgium

Facility Name

Tom Baker Cancer Centre-Calgary

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 4N2

Country

Canada

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1Z5

Country

Canada

Facility Name

Universitaet Duisburg-Essen

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Beatson West of Scotland Cancer Centre

City

Glasgow

ZIP/Postal Code

G12 0YN

Country

United Kingdom

Facility Name

Royal Marsden Hospital - Institute of Cancer Research - Chelsea

City

London

ZIP/Postal Code

SE3 6JJ

Country

United Kingdom

Facility Name

Plymouth Hospitals NHS Trust - Derriford Hospital

City

Plymouth

Country

United Kingdom

Facility Name

Royal Marsden Hospital - Institute of Cancer Research - Sutton

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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).

Learn more about this trial

We'll reach out to this number within 24 hrs