Clinical trial NCT05315713: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma, Follicular Lymphoma
Keywords: B-Cell Non-Hodgkin Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Adverse Events - Phase 1b
timeFrame: From the start of treatment until 90 days after the final dose of study treatment (up to 36 weeks)
measure: Best Objective Response Rate (ORR) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2
timeFrame: Up to Cycle 17 (cycle length = 21 days)
Secondary outcomes:
measure: Best ORR as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b
timeFrame: 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)
measure: Serum Concentration of Mosunetuzumab - Phase 1b
timeFrame: Cycle 1 Day 1 - Cycle 8 Day 1 (cycle length = 21 days)
measure: Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b
timeFrame: 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)
measure: Duration of Response (DOR) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b and Phase 2
timeFrame: 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)
measure: Progression-Free Survival (PFS) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2
timeFrame: 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)
measure: Event-Free Survival (EFS) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 2
timeFrame: 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)
measure: Overall Survival (OS) - Phase 2
timeFrame: From the time of first study treatment to death from any cause (up to approximately 4 years)
measure: Percentage of Participants With Adverse Events - Phase 2
timeFrame: From the start of treatment until 90 days after the final dose of study treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge Oostende AV
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Yvoir
country: Belgium
facility: CHU UCL Namur - Mont-Godinne
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre-Calgary
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Essen
country: Germany
facility: Universitaet Duisburg-Essen
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Institute of Cancer Research - Chelsea
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust - Derriford Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Institute of Cancer Research - Sutton
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: