The study will enroll approximately 380 participants with aggressive B-cell malignancies and indolent B-cell malignancies.
Inclusion Criteria
Participants with relapsed or refractory disease:
-Mantle cell lymphoma who have received at least 2 prior therapies including a BTKi, and are either post CAR-T cell therapy or ineligible for CAR-T cell therapy (Cohort A);
-Richter transformation who have received at least 1 prior therapy (Cohort B);
-Mantle cell lymphoma who have received at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi (Cohort C);
-Follicular lymphoma, or chronic lymphocytic leukemia who have received at least 2 prior systemic therapies and have no other available therapy (Cohorts D, E, and F);
- Chronic lymphocytic leukemia who have received at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi (Cohort G)
Exclusion Criteria
1. Has received solid organ transplant at any time.
2. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke, myocardial infarction or unstable angina <6 months prior to enrollment; congestive heart failure or serious cardiac arrhythmia requiring medication.
3. In participants with prior allo-SCT, acute GVHD or ongoing evidence of chronic GVHD manifesting as Grade ≥2 serum bilirubin, Grade ≥3 skin involvement, or Grade ≥3 diarrhea or requiring systemic immunosuppression for treatment/prophylaxis for their GVHD
Study Requirements
Each participant will participate in the study from the time the participant provides documented informed consent through the final contact. After a screening phase of up to 28 days, each participant will receive assigned intervention: each recipient of zilovertamab vedotin will receive the assigned intervention until disease progression, unacceptable toxicity, or other discontinuation criteria is achieved and each recipient of nemtabrutinib will receive the assigned intervention until disease progression, unacceptable toxicity, or other discontinuation criteria is achieved. After the end-of-treatment each participant will be followed for the occurrence of adverse events and spontaneously reported pregnancy. Participants who discontinue for reasons other than radiographic disease progression will have posttreatment follow-up scans for disease status until any of the conditions for discontinuation of imaging are met. All participants will be followed for overall survival until death, withdrawal of consent, or the end of the study.
