A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
Running, not enrolling · Phase 2
Conditions studied: Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Follicular Lymphoma, Richter Transformation Lymphoma
In brief
The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell lymphomas including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as monotherapy and in combination with respect to objective response rate. * Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy * Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy * Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi * Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy * Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR). As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)). As of Amendment 09, no additional participants with RT will be enrolled in Cohort B; however, those currently enrolled will continue with study intervention treatment (if applicable) until a protocol specified discontinuation criterion is met. Cohort E will be closed, as no participants with FL have been treated in this cohort.
Key facts
- Study ID
- NCT05458297
- Run by
- Merck Sharp & Dohme LLC
- People needed
- 189
- Starts
- 2022-07-21
- Expected to finish
- 2029-05-17
- Last updated by the study team
- 2026-08-07
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 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.
You may not qualify if…
- 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 not well controlled on antiretroviral therapy (ART)
- Active HBV or hepatitis C virus (HCV) infection.
- For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.
Where it is running
- Banner MD Anderson Cancer Center ( Site 0040) — Gilbert, Arizona, United States
- Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036) — Phoenix, Arizona, United States
- University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008) — Aurora, Colorado, United States
- Cancer Care Specialists of Illinois ( Site 0031) — Decatur, Illinois, United States
- University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics ( Site 0038) — Fairway, Kansas, United States
- Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007) — Saint Matthews, Kentucky, United States
- Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010) — Baltimore, Maryland, United States
- Tufts Medical Center ( Site 0024) — Boston, Massachusetts, United States
- Massachusetts General Hospital ( Site 0018) — Boston, Massachusetts, United States
- Dana-Farber Cancer Institute-Lymphoma ( Site 0026) — Boston, Massachusetts, United States
- University of Michigan ( Site 0009) — Ann Arbor, Michigan, United States
- Henry Ford Hospital ( Site 0035) — Detroit, Michigan, United States
- Icahn School of Medicine at Mount Sinai ( Site 0023) — New York, New York, United States
- Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0014) — Fargo, North Dakota, United States
- The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0004) — Columbus, Ohio, United States
- Avera Cancer Institute- Research ( Site 0011) — Sioux Falls, South Dakota, United States
- Medical Oncology Associates, PS ( Site 0005) — Spokane, Washington, United States
- University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030) — Madison, Wisconsin, United States
- Medical College of Wisconsin ( Site 0021) — Milwaukee, Wisconsin, United States
- Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1807) — Natal, Rio Grande do Norte, Brazil
- Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( Site 1809) — Rio de Janeiro, Brazil
- ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1808) — São Paulo, Brazil
- Hospital Paulistano-Americas Oncologia ( Site 1805) — São Paulo, Brazil
- BC Cancer Vancouver-Clinical Trials Unit ( Site 0201) — Vancouver, British Columbia, Canada
- Alaska Oncology and Hematology ( Site 0037) — Anchorage, Alaska, United States
Full record on ClinicalTrials.gov
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