Non-Hodgkin Lymphoma, Follicular Lymphoma
Conditions
Keywords
B-Cell Non-Hodgkin Lymphoma
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.
Interventions
DRUGMosunetuzumab SC
Participants will receive SC mosunetuzumab for up to 17 treatment cycles (cycle length = 21 days)
DRUGTiragolumab
Participants will receive IV tiragolumab every 3 weeks (Q3W) for up to 17 treatment cycles (cycle length = 21 days)
DRUGAtezolizumab
Participants will receive IV atezolizumab Q3W for up to 17 treatment cycles (cycle length = 21 days)
OTHERTocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Best ORR 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) | 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. |
| 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 | — |
| 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) | — |
| Serum Concentration of Mosunetuzumab - Phase 1b | Cycle 1 Day 1 - Cycle 8 Day 1 (cycle length = 21 days) | — |
Countries
Australia, Belgium, Canada, Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab Participants received SC mosunetuzumab on Cycle (C) 1 Day (D) 1, C1D8, C1D15, and on the first day of each subsequent 21-day treatment cycle. Participants also received IV tiragolumab every 3 weeks (Q3W). | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Progressive disease | 1 |
| Overall Study | Study terminated by sponsor | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab |
|---|---|
| Age, Continuous | 64.9 Years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
Primary
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)
Population: This endpoint was not evaluated due to early study termination (Phase 2 did not occur and no data was collected).
Primary
Percentage of Participants With Adverse Events - Phase 1b
Time frame: From the start of treatment until 90 days after the final dose of study treatment (up to 36 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Percentage of Participants With Adverse Events - Phase 1b | 100 Percentage of participants |
Secondary
Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b
Time frame: 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Best Complete Response (CR) Rate as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b | 37.5 Percentage of participants |
Secondary
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.
Time frame: 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Best ORR as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b | 62.5 Percentage of participants |
Secondary
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)
Population: Phase 1b is reported. No data was collected for Phase 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Duration of Response (DOR) as Determined by the Investigator Using Lugano 2014 Criteria - Phase 1b and Phase 2 | NA Time |
Secondary
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)
Population: This endpoint was not evaluated due to early study termination (Phase 2 did not occur and no data was collected).
Secondary
Overall Survival (OS) - Phase 2
Time frame: From the time of first study treatment to death from any cause (up to approximately 4 years)
Population: This endpoint was not evaluated due to early study termination (Phase 2 did not occur and no data was collected).
Secondary
Percentage of Participants With Adverse Events - Phase 2
Time frame: From the start of treatment until 90 days after the final dose of study treatment
Population: This endpoint was not evaluated due to early study termination (Phase 2 did not occur and no data was collected).
Secondary
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)
Population: This endpoint was not evaluated due to early study termination (Phase 2 did not occur and no data was collected).
Secondary
Serum Concentration of Mosunetuzumab - Phase 1b
Time frame: Cycle 1 Day 1 - Cycle 8 Day 1 (cycle length = 21 days)
Population: The PK population included all participants with at least one serum sample post-dose for mosunetuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D1 pre-dose | NA ug/mL | — |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D1 3 hrs post-dose | 0.00983 ug/mL | — |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D2 24 hrs post-dose | 0.0556 ug/mL | Geometric Coefficient of Variation 109.6 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D4 72 hrs post-dose | 0.164 ug/mL | Geometric Coefficient of Variation 90.5 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D8 pre-dose | 0.166 ug/mL | Geometric Coefficient of Variation 83.2 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C1D15 pre-dose | 2.18 ug/mL | Geometric Coefficient of Variation 48.8 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C2D1 pre-dose | 4.02 ug/mL | Geometric Coefficient of Variation 86.3 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C3D1 pre-dose | 2.90 ug/mL | Geometric Coefficient of Variation 81.8 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C4D1 pre-dose | 2.34 ug/mL | Geometric Coefficient of Variation 49 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C4D1 3 hrs post-dose | 2.10 ug/mL | Geometric Coefficient of Variation 48.2 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C5D1 pre-dose | 2.59 ug/mL | Geometric Coefficient of Variation 25.7 |
| Subcutaneous (SC) Mosunetuzumab in Combination With Intravenous (IV) Tiragolumab | Serum Concentration of Mosunetuzumab - Phase 1b | C8D1 pre-dose | 2.97 ug/mL | Geometric Coefficient of Variation 17.7 |