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

Purpose

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)).

Conditions

  • Chronic Lymphocytic Leukemia
  • Mantle Cell Lymphoma
  • Follicular Lymphoma
  • Richter Transformation Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy
Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140
Experimental
Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy
Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140
Experimental
Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy
Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation.
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140
  • Drug: Nemtabrutinib
    Oral tablet
    Other names:
    • MK-1026
Experimental
Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy
Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140
Experimental
Cohort E, Relapsed or Refractory FL with 2 Prior Lines of Therapy
Participants will receive either zilovertamab vedotin IV infuison Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140

Recruiting Locations

Banner MD Anderson Cancer Center ( Site 0040)
Gilbert 5295903, Arizona 5551752 85234
Contact:
Study Coordinator
480-256-6444

Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
Phoenix 5308655, Arizona 5551752 85006
Contact:
Study Coordinator
480-256-6444

University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008)
Aurora 5412347, Colorado 5417618 80045
Contact:
Study Coordinator
720-848-0300

Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
Saint Matthews 4307238, Kentucky 6254925 40207
Contact:
Study Coordinator
888-577-8839

Tufts Medical Center ( Site 0024)
Boston 4930956, Massachusetts 6254926 02111
Contact:
Study Coordinator
617-636-2675

Massachusetts General Hospital ( Site 0018)
Boston 4930956, Massachusetts 6254926 02114
Contact:
Study Coordinator
617-571-3037

Dana-Farber Cancer Institute-Lymphoma ( Site 0026)
Boston 4930956, Massachusetts 6254926 02215
Contact:
Study Coordinator
617-632-6844

University of Michigan ( Site 0009)
Ann Arbor 4984247, Michigan 5001836 48109
Contact:
Study Coordinator
888-577-8839

Henry Ford Hospital ( Site 0035)
Detroit 4990729, Michigan 5001836 48202
Contact:
Study Coordinator
313-725-7856

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0004)
Columbus 4509177, Ohio 5165418 43210
Contact:
Study Coordinator
888-577-8839

Avera Cancer Institute- Research ( Site 0011)
Sioux Falls 5231851, South Dakota 5769223 57105
Contact:
Study Coordinator
888-577-8839

Medical Oncology Associates, PS ( Site 0005)
Spokane 5811696, Washington 5815135 99208
Contact:
Study Coordinator
509-462-2275

University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030)
Madison 5261457, Wisconsin 5279468 53792
Contact:
Study Coordinator
888-577-8839

More Details

NCT ID
NCT05458297
Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com