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IC La Serena Research | La Serena, Chile

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

Merck Sharp & Dohme (MSD) logo

Merck Sharp & Dohme (MSD)

Status and phase

Enrolling
Phase 2

Conditions

Follicular Lymphoma
Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia
Richter Transformation Lymphoma

Treatments

Biological: Zilovertamab vedotin
Drug: Nemtabrutinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT05458297
jRCT2011230019 (Registry Identifier)
2140-006
MK-2140-006 (Other Identifier)
2021-004450-36 (EudraCT Number)

Details and patient eligibility

About

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
  • Cohort F: Participants with relapsed or refractory CLL 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).

Enrollment

275 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

The main inclusion criteria include, but are not limited to the following:

Inclusion Criteria:

  • For aggressive B-cell malignancies 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 FL and 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 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

275 participants in 6 patient groups

Cohort A
Experimental group
Description:
Participants will receive zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) until disease progression or discontinuation.
Treatment:
Biological: Zilovertamab vedotin
Cohort B
Experimental group
Description:
Participants will receive zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) until disease progression or discontinuation.
Treatment:
Biological: Zilovertamab vedotin
Cohort C
Experimental group
Description:
Participants will receive zilovertamab vedotin every 3 weeks (Q3W) combined with nemtabrutinib daily until disease progression or discontinuation.
Treatment:
Drug: Nemtabrutinib
Biological: Zilovertamab vedotin
Cohort D
Experimental group
Description:
Participants will receive either zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) or 2.0 mg/kg with infusions on Days 1 and 8 of each 3 week cycle (Q2/3W) until disease progression or discontinuation.
Treatment:
Biological: Zilovertamab vedotin
Cohort E
Experimental group
Description:
Participants will receive either zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) or 2.0 mg/kg with infusions on Days 1 and 8 of each 3 week cycle (Q2/3W) until disease progression or discontinuation.
Treatment:
Biological: Zilovertamab vedotin
Cohort F
Experimental group
Description:
Participants will receive either zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) or 2.0 mg/kg with infusions on Days 1 and 8 of each 3 week cycle (Q2/3W) until disease progression or discontinuation.
Treatment:
Biological: Zilovertamab vedotin

Trial contacts and locations

106

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Central trial contact

Toll Free Number

Data sourced from clinicaltrials.gov

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