Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a Non-Randomized Single Arm US Extension of Mosunetuzumab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy
Overview
- Phase
- Phase 3
- Intervention
- Mosunetuzumab
- Conditions
- Not specified
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 478
- Locations
- 217
- Primary Endpoint
- Progression Free Survival (PFS) according to 2014 Lugano Response Criteria
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- •Histologically documented CD20+ FL (Grades 1-3a)
- •Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
- •Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
- •Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL. Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures may be eligible for study enrollment if an archival tumor tissue sample (preferably from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained slides, or in accordance with local regulatory requirements, can be sent to the Sponsor.
- •Adequate hematologic function (unless due to underlying lymphoma, per the investigator)
- •Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program.
- •For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 adequate methods of contraception, including at least 1 method with a failure rate of \< 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months after final dose of rituximab. Women must refrain from donating eggs during this same period.
- •For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 28 days after last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must refrain from donating sperm during this same period.
Exclusion Criteria
- •Grade 3b FL
- •Any history of disease transformation and/or diffuse-large B cell lymphoma (DLBCL)
- •Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
- •Active or history of CNS lymphoma or leptomeningeal infiltration
- •Prior standard or investigational anti-cancer therapy as specified: Lenalidomide exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Cycle 1 Day 1; Treatment with any anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
- •Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade \</= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0) prior to Day 1 of Cycle 1
- •Treatment with systemic immunosuppressive medications, including, but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
- •History of solid organ transplantation
- •History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies
- •Known sensitivity or allergy to murine products
Arms & Interventions
M + Len (Arm A)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Mosunetuzumab
M + Len (Arm A)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Lenalidomide
M + Len (Arm A)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Tociluzumab
R + Len (Arm B)
Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)
Intervention: Lenalidomide
R + Len (Arm B)
Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)
Intervention: Rituximab
R + Len (Arm B)
Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)
Intervention: Tociluzumab
M + Len (US Extension Arm C)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Mosunetuzumab
M + Len (US Extension Arm C)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Lenalidomide
M + Len (US Extension Arm C)
Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
Intervention: Tociluzumab
Outcomes
Primary Outcomes
Progression Free Survival (PFS) according to 2014 Lugano Response Criteria
Time Frame: From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8.5 years)
Secondary Outcomes
- Objective Response Rate (ORR)(Up to approximately 8.5 years)
- Overall Survival (OS)(From randomization to death from any cause (up to approximately 8.5 years))
- Duration of Objective Response (DOR)(From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years))
- Duration of Complete Reponse (DOCR)(From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years))
- Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)(Up to approximately 8.5 years)
- Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)(Up to approximately 8.5 years)
- PFS as Determined by the Investigator(From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8.5 years))
- Complete Response Rate(Up to approximately 8.5 years)
- Percentage of Participants with Adverse Events (AEs)(Up to approximately 8.5 years)
- Serum Concentration of M + Len(Up to approximately 8.5 years)
- Area Under the Curve (AUC) of M + Len(Up to approximately 8.5 years)
- Percentage of Participants with Anti-Drug Antibodies (ADAs)(Up to approximately 8.5 years)
- Time to New Anti-Lymphoma Treatment (TTNALT)(From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8.5 years))