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

January 25, 2024 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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
      • Nagoya, Aichi, Japan, 466-8560
        • Nagoya University Hospital ( Site 0003)
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • National Cancer Center Hospital East ( Site 0002)
    • Osaka
      • Osakasayama, Osaka, Japan, 589-8511
        • Kindai University Hospital ( Site 0006)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: Up to approximately 4 weeks
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)
Time Frame: Up to approximately 38 months
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
Time Frame: Up to approximately 38 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the Curve (AUC) of Nemtabrutinib
Time Frame: 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
AUC is the area under the curve of plasma concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine AUC.
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
Time Frame: 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
Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
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
Time Frame: 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
Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
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
Time Frame: 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
Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.
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
Time Frame: Up to approximately 38 months
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.
Up to approximately 38 months
Duration of Response (DOR) as Assessed by Investigator
Time Frame: Up to approximately 38 months
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 38 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2023

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

March 30, 2026

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)

January 26, 2024

Last Update Submitted That Met QC Criteria

January 25, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1026-002
  • MK-1026-002 (Other Identifier: Merck)
  • jRCT2031220583 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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