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

Conditions

• Chronic Lymphocytic Leukemia
• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Lymphoma, B-Cell
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Richter's Transformation
• Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Nemtabrutinib — DRUG
  Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.

Study Details

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.

Key Dates

Start date

Jun 26, 2017

Status verified

Aug 2025

Primary completion

Sep 18, 2026

Completion

Sep 18, 2026

Study Design

Enrollment

190 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1: Dose Escalation and Determination of RP2D
  Phase I: Dose Escalation and determination of RP2D, multiple dose levels of nemtabrutinib to be evaluated (Up to approximately 22 months).
• Experimental: Phase 2: Expansion Cohort A
  Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (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 BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until progressive disease (PD), unacceptable adverse events (AEs), or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion 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 receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort C
  Richter's transformation (RT) participants who have failed at least one prior therapy receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort D
  Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort E
  Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort F
  Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort G
  High-grade B-cell lymphoma (BCL) participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations confirmed by flourescence in situ hybridization (FISH) or overexpression by immunohistochemistry (IHC) receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Cohort H
  Waldenström macroglobulinemia (WM) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).
• Experimental: Phase 2: Expansion Food Effect Cohort I
  B-cell Non-Hodgkin's lymphoma (NHL), CLL/SLL and WM participants receive up to 65 mg of nemtabrutinib fasted (1 hour prior to or 2 hours after meal) and non-fasted per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Primary Outcome Measure

Phase 1: Number of Participants Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (up to 28 days) ]

Locations (10)

Find similar trials in Scottsdale, AZ

Related Studies

• Family Study of Lymphoproliferative Disorders
  Recruiting · Mayo Clinic · Rochester, Minnesota
• A Long-term Extension Study of PCI-32765 (Ibrutinib)
  PHASE3 · Recruiting · Janssen Research & Development, LLC · Duarte, California
• Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
  PHASE1 · Recruiting · Baylor College of Medicine · Houston, Texas
• The Prospective Collection, Storage and Reporting of Data on Patients Undergoing Hematopoietic Stem Cell Transplantation Utilizing a Standard Preparative Regimen
  Recruiting · Wake Forest University Health Sciences · Winston-Salem, North Carolina