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A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001) | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)

A Phase 1/2 Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of ARQ 531 in Selected Subjects With Relapsed or Refractory Hematologic Malignancies

NCT03162536•ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

View on ClinicalTrials.gov

Summary

This study aims to evaluate the safety, tolerability, pharmacodynamic, and pharmacokinetic (PK) of nemtabrutinib (formerly ARQ 531) tablets in selected participants with relapsed or refractory hematologic malignancies. No formal hypothesis testing will be performed for this study.

Detailed Description

This study includes 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion). In Phase 1, participants will enroll using 3+3 dose escalation design. The starting dose of nemtabrutinib in oral tablet form was 5mg/day continuously. Dose escalation will continue until the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and dosing schedule is reached based on protocol-defined dose limiting toxicity (DLT). After the determination of the RP2D, 9 expansion cohorts will be initiated to evaluate the safety, tolerability, and efficacy of nemtabrutinib at RP2D in participants with specifically defined disease.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Signed written informed consent granted prior to initiation of any study-specific procedures
•For the dose escalation cohorts, relapsed or refractory (R/R) participants with a diagnosis of B-cell Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and Waldenstrom macroglobulinemia (WM) who have received at least two prior systemic therapies . Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Participants with low grade lymphoma must be progressing and requiring treatment
•For the expansion cohorts, the following criteria must be met:
•* Cohort A: R/R CLL/SLL participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented Bruton's tyrosine kinase (BTK) mutation on C481 residue
•* Cohort B: R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue. In this study, intolerance to standard therapy is defined as having experienced a grade 3 or higher adverse event that was caused by the standard therapy and resulted in treatment discontinuation
•* Cohort C: Richter's transformation (RT) participants who have failed at least one prior therapy
•* Cohort D: Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A
•* Cohort E: Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies
•* Cohort F: Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies
•* Cohort G: High-grade B-cell lymphoma participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations
+17 more criteria

Exclusion Criteria

•Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 5 half-lives or four weeks (whichever is shorter) prior to treatment initiation, or oral therapy within 5 half-lives or one week (whichever is shorter) prior to treatment initiation
•Transformation of follicular lymphoma (FL) to a more aggressive subtype of lymphoma or grade 3b FL
•Participants currently being treated with the following drugs:
•* CYP2C8 substrates with a narrow therapeutic index (such as paclitaxel)
•* P-gp substrates with a narrow therapeutic index (such as digoxin)
•* CYP3A strong inducers (such as rifampin) Note: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment
•Active central nervous system (CNS) involvement
•Pregnant or breast-feeding women
•Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug
•Uncontrolled illness including but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in the past six months, and psychiatric illness that would limit compliance with study requirements
+4 more criteria

Locations (10)

Mayo Clinic Hospital ( Site 0140)

Scottsdale, Arizona, United States

UCLA Hematology & Oncology ( Site 0017)

Los Angeles, California, United States

Colorado Blood Cancer Institute ( Site 0225)

Denver, Colorado, United States

University of Michigan ( Site 0018)

Ann Arbor, Michigan, United States

Mayo Clinic - Rochester ( Site 0138)

Rochester, Minnesota, United States

Duke Cancer Center ( Site 0067)

Durham, North Carolina, United States

The Ohio State University Wexner Medical Center ( Site 0056)

Columbus, Ohio, United States

Tennessee Oncology, PLLC ( Site 0020)

Nashville, Tennessee, United States

UT Southwestern Medical Center ( Site 0116)

Dallas, Texas, United States

University of Utah, Huntsman Cancer Institute ( Site 0122)

Salt Lake City, Utah, United States

Key Dates

Start Date

June 26, 2017

Primary Completion Date

September 18, 2026

Completion Date

September 18, 2026

Last Updated

September 8, 2025

Enrollment

190

ESTIMATED participants

Conditions

Lymphoma, B-CellSmall Lymphocytic LymphomaChronic Lymphocytic LeukemiaWaldenstrom MacroglobulinemiaMantle Cell LymphomaDiffuse Large B Cell LymphomaRichter's TransformationFollicular LymphomaMarginal Zone Lymphoma

Interventions

Nemtabrutinib

DRUG

A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia

NCT07277231

Chronic Lymphocytic Leukemia

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RECRUITINGPHASE1/PHASE2

A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

NCT05006716

B-cell MalignancyMarginal Zone Lymphoma+7 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 8, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)

Inclusion Criteria

Exclusion Criteria

A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia

A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

A Long-term Extension Study of PCI-32765 (Ibrutinib)

A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: