NCT06006117

Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma

Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 260 (estimated)
• Sponsor: The Lymphoma Academic Research Organisation · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label, multi-center, international, randomized phase III trial to compare the efficacy of Mosunetuzumab-Lenalidomide with investigator choices exclusively in R/R MZL patients. Patients with a proven diagnosis of EMZL, SMZL or NMZL subtypes and previously treated with at least one prior systemic treatment and not more than three prior lines are eligible. Previous treatment line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib. The patients will be Randomized as follows: Arm A - Experimental arm: • Mosunetuzumab-Lenalidomide Arm B - Comparator arms ( Investigator Choices): * Rituximab-Lenalidomide * Rituximab-Bendamustine * Rituximab-CHOP

Detailed description

This is an open label, multi-center, international, randomized phase III trial to compare the efficacy of Mosunetuzumab-Lenalidomide with investigator choices exclusively in R/R MZL patients. Patients with a proven diagnosis of EMZL, SMZL or NMZL subtypes and previously treated with at least one prior systemic treatment and not more than three prior lines are eligible. Previous treatment line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib. Patients are stratified according to MZL subtypes and time to progression of disease after first-line within 2 years (POD24) \< 2 years or \> 2 years. Mosunetuzumab will be administered sub-cutaneously (SC) (21 days first cycle, then 28 days next cycles) and Lenalidomide will be given PO 20 mg/day from Day 1 to Day 21 from cycles C2 to C6. For each patient, investigator choice had to be decided before randomization between Rituximab-Lenalidomide and Rituximab-chemotherapy (R-Bendamustine or R-CHOP). The primary efficacy endpoint for comparison is the Progression-free survival (PFS) as determined by investigator (Lugano criteria 2014). Secondary objectives include CR24 as determined by investigator (at 24 months) according to Lugano criteria 2014 and by central review based on PET result, Overall response rate (ORR) and CR other than CR24 as determined by investigator, or by central review based on PET result according to Lugano Criteria 2014. 260 patients are planned to be enrolled in France, Belgium, Germany, Italy and Portugal

Conditions

• Marginal Zone Lymphoma

Interventions

Type	Name	Description
DRUG	Mosunetuzumab (SC)	○ Mosunetuzumab will be administered SC (21 days first cycle, then 28 days next cycles) * C1 (21-days cycle): step-up dosing schedule 5 mg Day 1, 45 mg on Day 8 and 45 mg Day 15 * C2 to C12: 45 mg D1 28-days cycles
DRUG	Rituximab (R)	Rituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12
DRUG	Bendamustine	○ Bendamustine IV 70 or 90 mg/m² (according to the investigator's judgment) D1 and D2/28 days x 6 cycles 28 days cycles). For patients in complete response (CR) at 3 cycles, Bendamustine and Rituximab could be stopped after 4 cycles at investigator discretion
DRUG	CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)	CHOP, IV standard dose from cycle 1 to 6
DRUG	Lenalidomide	Cycles 2 to 6 (28-day cycles): starting dose is based on patient's creatinine clearance, from day 1 to day 21, once a day, rest period from day 22 to day 28

Timeline

• Start date: 2023-09-05
• Primary completion: 2027-09-01
• Completion: 2032-09-01
• First posted: 2023-08-23
• Last updated: 2025-12-19

Locations

48 sites across 5 countries: Belgium, France, Germany, Italy, Portugal