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
Have a biopsy proven diagnosis of MZL, extranodal (EMZL) or nodal (NMZL) Or have a diagnosis of splenic MZL (SMZL) based on mandatory 13 flow cytometry markers: surface immunoglobulins (SmIg), CD5, CD23, FMC7, CD22 or CD79b, CD200, CD180, CD20, CD43, CD11c, CD10,CD103 and CD123 and validated by a centralized review.
Have been treated with at least one prior systemic treatment and not more than three prior lines. Previous line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles; participants treated with monoclonal antibody monotherapy should have received at least 4 weekly injections) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as BTK inhibitors (at least 1 month). Participants previously treated by lenalidomide are eligible if the last administration of lenalidomide is superior to 12 months before C1D1. When randomized in comparator arm, those participants should require R-chemo. Prior local therapy (including surgery, radiotherapy antibiotics for H. pylori-positive gastric lymphoma, and antiviral for hepatitis C virus) is not considered as one line of treatment
Signed Informed Consent Form
Age ≥ 18 years at the time of signing the informed consent form
MZL with histologic transformation to high-grade lymphoma
Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies
Allogeneic stem cell transplant
Radiotherapy within 2 weeks prior to the first dose of study treatment
Parallel
Mosunetuzumab (SC)
Drug○ 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
Rituximab (R)
DrugRituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12
Bendamustine
Drug○ 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
CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)
DrugCHOP, IV standard dose from cycle 1 to 6
Lenalidomide
DrugCycles 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
Progression-free survival (PFS) as determined by investigator
according to Lugano criteria 2014
Complete Response rate (CR) as determined by investigator (CR24)
according to Lugano criteria 2014
Complete response rate (CR) by blinded central review (CR24)
based on PET result according to Lugano Criteria 2014
Overall response rate (ORR) as determined by investigator
according to Lugano Criteria 2014
Overall response rate (ORR) as determined by investigator
according to Lugano Criteria 2014
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