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

Phase 1

Active, not recruiting

• Conditions: Mature B-cell Neoplasms
• Interventions: Drug: Nemtabrutinib

• Registration Number: NCT05673460
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-04
• Study First Submitted QC: 2023-01-04
• Study First Posted: 2023-01-06
• Study Start: 2023-02-13
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-26
• Primary Completion: 2026-03-30
• Study Completion: 2026-03-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Participants who Experience Adverse Events (AEs)	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.
Number of Participants who Experience Dose Limiting Toxicities (DLTs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0	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.
Number of Participants Discontinuing Study Treatment due to AEs	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.

Secondary Outcome Measures

Name	Time	Method
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	AUC is the area under the curve of plasma concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine AUC.
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	Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
Objective Response Rate (ORR) as Assessed by Investigator	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.
Duration of Response (DOR) as Assessed by Investigator	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.
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	Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
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	Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.

Trial Locations

Locations (7)

National Cancer Center Hospital East ( Site 0002); 🇯🇵 Kashiwa, Chiba, Japan

Kyushu University Hospital ( Site 0008); 🇯🇵 Fukuoka, Japan

Chiba Cancer Center ( Site 0005); 🇯🇵 Chiba, Japan

Yamagata University Hospital ( Site 0001); 🇯🇵 Yamagata, Japan

Okayama University Hospital ( Site 0007); 🇯🇵 Okayama, Japan

Nagoya University Hospital ( Site 0003); 🇯🇵 Nagoya, Aichi, Japan

Kindai University Hospital ( Site 0006); 🇯🇵 Osakasayama, Osaka, Japan