Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (NHL)
Conditions
Interventions
Product Name: Mosunetuzumab
Product Code: RO7030816
Pharmaceutical Form: Solution for injection
INN or Proposed INN: MOSUNETUZUMAB
Current Sponsor code: RO7030816
Concentration unit: mg/ml milligram(s
Sponsors
F. Hoffman-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - Participants who have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 - Participants who have a life expectancy of at least 12 weeks 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). - Participants who have histologically documented FL or DLBCL that expresses CD20 as determined by the local laboratory. - Participants who have at least one bi-dimensionally measurable (>1.5 cm) nodal lesion, or at least one bi-dimensionally measurable (>1.0 cm) extranodal lesion - Participants who have confirmed availability of a tumor tissue - Participants with FL for whom a bone marrow biopsy and aspirate can be collected - Participants with adequate hematologic and organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 118 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 118
Exclusion criteria
Exclusion criteria: Participants who have received any of the following treatments prior to study entry: o Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies o Treatment with tiragolumab or other anti- T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains agent o Allogeneic stem Cell Transplant (SCT) o Solid organ transplantation - Participants who received any of the following treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment: o Radiotherapy within 2 weeks prior to the first dose of study treatment If participants have received radiotherapy within 4 weeks prior to the first study treatment administration, participants must have at least one measurable lesion outside of the radiation field. o Autologous SCT within 100 days prior to first study treatment o Chimeric antigen receptor T-cell therapy within 30 days before first study treatment o Use of monoclonal antibodies or antibody-drug conjugates for the treatment of lymphoma, within 4 weeks prior to first study treatment o Use of radioimmunoconjugates within 12 weeks prior to first study treatment o Systemic immunosuppressive medications within 2 weeks prior to first dose of study treatment o Any other anti-cancer therapy, whether investigational or approved o The Medical Monitor should be informed of any prior cancer immunotherapy not explicitly described in this protocol - Participants who received a live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment - Participants with aggressive NHL who are currently eligible for autologous SCT - Participants with current or past history of CNS lymphoma or leptomeningeal infiltration - Participants with a history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy - Participants with a contraindication to atezolizumab (specific to Arm 2 of the study ) or tocilizumab - Participants in whom clinically significant toxicities from prior treatment have not resolved to Grade <= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) prior to the first study drug administration - Participants with treatment-emergent immune-mediated adverse events associated with prior immunotherapeutic agents - Participants with evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results - Participants who underwent recent major surgery within 4 weeks prior to first study treatment administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b •To evaluate the safety of mosunetuzumab subcutaneous (SC) in combination with tiragolumab intravenous (IV) with or without atezolizumab IV, including evaluation of the tolerability of the dosing schedule and dose, and characterization of dose limiting toxicities (DLTs). Phase 2 •To evaluate the efficacy of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants with R/R FL and R/R DLBCL. ;Secondary Objective: Phase 1b •To evaluate the preliminary efficacy of mosunetuzumab SC in combination with tiragolumab with or without atezolizumab IV Phase 2 •To evaluate the efficacy of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants with R/R FL. Phase 2 - secondary safety objectives •To evaluate the efficacy and safety of mosunetuzumab SC in combination with tiragolumab IV in participants with R/R FL and DLBCL, and mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV in participants with R/R FL Phase 1b and 2 •To characterize the PK profile of mosunetuzumab SC in combination with tiragolumab IV •To characterize the PK profile of mosunetuzumab SC in combination with tiragolumab IV and atezolizumab IV ;Primary end point(s): Phase Ib 1.Incidence and severity of adverse events, including DLTs, with severity determined according to NCI CTCAE v5.0; for CRS, severity determined according to American Society for Transplantation and Cellular Therapy cytokine-release syndrome consensus grading criteria Phase 2 2.Best objective response rate as determined by the investigator using Lugano 2014 criteria ;Timepoint(s) of evaluation of this end point: 1.Until 90 days after the final | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib 1. Best objective response rate* 2. Best complete response rate* 3. Duration of response* Phase 2 4. Best complete response rate* 5. Duration of response* 6. Progression free survival* 7. Event-free survival* 8. Overall survival 9. Occurrence and severity of adverse events, with severity determined according to NCI CTCAE v5.0. For CRS, severity determined according to the ASTCT CRS Consensus Grading criteria *as determined by the investigator using Lugano 2014 criteria;Timepoint(s) of evaluation of this end point: 1-8. Up to 36 Months 9. Until 90 days after the final dose of study treatment | — |
Countries
Australia, Belgium, Canada, Germany, New Zealand, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffman-La Roche Ltd
Outcome results
None listed