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

Study Overview
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Brief Summary
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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.

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

Conditions
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Mature B-cell Neoplasms

Intervention / Treatment
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* Drug: Nemtabrutinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Curve (AUC) of Nemtabrutinib | 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 | 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 | 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 | 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 | 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 | 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 |