A Clinical Study of Nemtabrutinib in Japanese Participants With Hematological Malignancies (MK-1026-002)

NCT05673460 | Completed Phase 1 FDA Drug

• 3 other identifiers: 1026-002MK-1026-002jRCT2031220583
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of nemtabrutinib in Japanese participants with mature B-cell neoplasms.

Conditions

Mature B-cell Neoplasms

Outcome Measures

Primary Outcomes (3)

• Number of Participants who Experience Dose Limiting Toxicities (DLTs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  A DLT consists of one or more of the following toxicities: Grade ≥3 nonhematologic toxicity with exception of Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension; Grade 4 hematologic toxicity lasting \>7 days, Grade 4 platelet count decreased of any duration (with exceptions), or Grade 3 platelet count decreased with bleeding, or Grade 3 or higher febrile neutropenia of any duration; Grade 3 or Grade 4 nonhematologic laboratory abnormality, if values result in drug induced liver injury (DILI), or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib doses as a result of drug-related AE(s); Grade 5 toxicity. Toxicities will be graded using NCI-CTCAE version 5.0 except hematologic toxicities in participants with chronic lymphocytic leukemia (CLL) assessed according to the International Workshop on CLL (iwCLL) criteria.

  Up to approximately 4 weeks

• Number of Participants who Experience Adverse Events (AEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 38 months

• Number of Participants Discontinuing Study Treatment due to AEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 38 months

Secondary Outcomes (6)

• Area under the Curve (AUC) of Nemtabrutinib

  Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days

• Maximum Concentration (Cmax) of Nemtabrutinib

  Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days

• Time to Maximum Concentration (Tmax) of Nemtabrutinib

  Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days

• Minimum Concentration (Cmin) of Nemtabrutinib

  Day 1 of Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days

• Objective Response Rate (ORR) as Assessed by Investigator

  Up to approximately 38 months

Study Arms (1)

Nemtabrutinib

EXPERIMENTAL

Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation

Drug: Nemtabrutinib

Interventions

Nemtabrutinib DRUG

Nemtabrutinib tablets will be administered orally QD at dosage of 45 mg or 65 mg

Also known as: MK-1026, ARQ 531

Nemtabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Histologically confirmed B-cell malignancy:
• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Waldenström's macroglobulinemia (WM),
• Lymphoplasmacytic lymphoma (LPL)
• Other B-cell neoplasm
• Failed or intolerant to either at least 2 prior regimens given in combination or sequentially OR have received 1 prior Bruton's tyrosine kinase (BTK)-containing regimen when a BTK inhibitor is approved as first line therapy
• Have the ability to swallow and retain oral medication
• Is Japanese
• Active Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection at study entry
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
• Known history of human immunodeficiency virus (HIV) infection
• Clinically significant gastrointestinal abnormalities that might alter absorption (eg, gastric bypass surgery, gastrectomy)
• Underlying history of severe bleeding disorders
• History or concurrent condition of pneumonitis/interstitial lung disease

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (7)

Nagoya University Hospital ( Site 0003)

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Cancer Center Hospital East ( Site 0002)

Kashiwa, Chiba, 2778577, Japan

Location

Kindai University Hospital ( Site 0006)

Sayama, Osaka, 589-8511, Japan

Location

Chiba Cancer Center ( Site 0005)

Chiba, 260-8717, Japan

Location

Kyushu University Hospital ( Site 0008)

Fukuoka, 812-8582, Japan

Location

Okayama University Hospital ( Site 0007)

Okayama, 700-8558, Japan

Location

Yamagata University Hospital ( Site 0001)

Yamagata, 990-9585, Japan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

ARQ531

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 6, 2023
• Study Start: February 13, 2023
• Primary Completion: April 28, 2025
• Study Completion: September 3, 2025
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

JP (7)