A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)

Launched by MERCK SHARP & DOHME LLC · Jul 11, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called zilovertamab vedotin for patients with certain types of B-cell lymphomas, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Richter transformation lymphoma (RTL). The goal of the study is to see how safe this treatment is and how effective it can be on its own or when combined with other therapies. Participants must have already tried at least one or two other treatments that didn't work for them. The trial is open to adults aged 65 and older who meet specific health criteria, including having a confirmed diagnosis of one of the targeted lymphomas.

If you join the trial, you'll receive zilovertamab vedotin, and the doctors will closely monitor your health and response to the treatment. This study is important because it aims to provide new options for patients who have not responded to previous therapies. Before participating, it's essential to check if you meet the eligibility requirements, which include factors like your previous treatments and overall health. The trial is currently recruiting participants, so if you think you might be eligible, please discuss this with your healthcare team.

Gender

ALL

Eligibility criteria

• The main inclusion criteria include, but are not limited to the following:
• Inclusion Criteria:
• • For aggressive B-cell malignancies mantle cell lymphoma (MCL): 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 C: 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 Eastern Cooperative Oncology Group (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 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 within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was 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.
• • 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.