A research study to evaluate the safety and effectiveness of Zilovertamab Vedotin with or without Nemtabrutinib in adults with B-cell Malignancies

Phase 1

Recruiting

• Conditions: Aggressive and Indolent B-cell Malignancies (mantle cell lymphoma; chronic lymphocytic leukemia; follicular lymphoma; Richter’s syndrome); MedDRA version: 21.0Level: LLTClassification code: 10008976Term: Chronic lymphocytic leukemia Class: 10029104; MedDRA version: 20.0Level: PTClassification code: 10058728Term: Richter's syndrome Class: 100000004864; MedDRA version: 20.0Level: PTClassification code: 10061275Term: Mantle cell lymphoma Class: 100000004864; MedDRA version: 24.0Level: PTClassification code: 10085128Term: Follicular lymphoma Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-501374-19-00
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-20
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

For aggressive B-cell malignancies mantle cell lymphoma (MCL) Cohort A: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton’s tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy, For aggressive B-cell malignancies MCL Cohort A: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi., For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease., For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy., Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation., Have an ECOG performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.

Exclusion Criteria

Has received solid organ transplant at any time., Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent., Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention., Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma., Has an active infection requiring systemic therapy., Has a known history of human immunodeficiency virus (HIV) infection., Active HBV or hepatitis C virus (HCV) infection., For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption., Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina (<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class =II), or serious cardiac arrhythmia requiring medication., Has pericardial effusion or clinically significant pleural effusion., Has ongoing Grade >1 peripheral neuropathy., Has a demyelinating form of Charcot-Marie-Tooth disease., Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years., Participants with FL who have transformed to a more aggressive type of lymphoma., Has received prior systemic anticancer therapy, including investigational agents, within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (small molecules like kinase inhibitors) prior to the first dose of study intervention., Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified