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

A Phase 1 Clinical Study of Nemtabrutinib (MK-1026) in Japanese Participants With Hematological Malignancies (BELLWAVE-002)

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

Study Overview

• Status: Completed
• Conditions: Mature B-cell Neoplasms
• Intervention / Treatment: Drug: Nemtabrutinib

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center ( Site 0005)
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0008)
  • Okayama, Japan, 700-8558
    • Okayama University Hospital ( Site 0007)
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital ( Site 0001)
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital ( Site 0003)
  • Chiba
    • Kashiwa, Chiba, Japan, 2778577
      • National Cancer Center Hospital East ( Site 0002)
  • Osaka
    • Sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0006)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nemtabrutinib; Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation	Drug: Nemtabrutinib; Nemtabrutinib tablets will be administered orally QD at dosage of 45 mg or 65 mg; Other Names: MK-1026; ARQ 531

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 is ≥1 of: Grade ≥3 nonhematologic toxicity with exception of Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension lasting >72 hours despite optimal supportive case; 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 (with exceptions), or Grade 3 or higher febrile neutropenia of any duration; Grade 3 or Grade 4 nonhematologic laboratory abnormality, if results 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 26 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 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Dosing to 24 Hours Postdose (AUC0-24) of Nemtabrutinib	AUC0-24 is the area under the curve of plasma concentration of nemtabrutinib from dosing to 24 hours postdose.	Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Minimum Concentration (Cmin) of Nemtabrutinib	Cmin is the lowest observed plasma concentration.	Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Maximum Concentration (Cmax) of Nemtabrutinib	Cmax is the lowest observed plasma concentration.	Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Time to Maximum Concentration (Tmax) of Nemtabrutinib	Tmax is the time to reach Cmax.	Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Objective Response Rate (ORR) as Assessed by Investigator	ORR is the proportion of participants in the analysis population with objective response. Objective response is defined as participants who achieve at least a partial response (PR) per disease-specific criteria as assessed by investigator. Data are presented separately for participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and non-CLL/SLL participants.	Up to approximately 26 months
Duration of Response (DOR) as Assessed by Investigator	For participants who demonstrate an objective response as assessed by investigator, per disease-specific criteria, duration of response is defined as the time from the first documented evidence of an objective response until disease progression or death due to any cause, whichever occurs first.	Up to approximately 26 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Actual): April 28, 2025
• Study Completion (Actual): September 3, 2025

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hematologic Neoplasms; Lymphoma, B-Cell; ARQ531
• Other Study ID Numbers: 1026-002; MK-1026-002 (Other Identifier: MSD); jRCT2031220583 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes