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

Mature B-cell Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05673460
• Other study ID #: 1026-002
• Secondary ID: MK-1026-002jRCT2
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 13, 2023
• Est. completion date: March 30, 2026

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: March 30, 2026
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Lymphoma, B-Cell
• Mature B-cell Neoplasms

Intervention

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

Locations

Country	Name	City	State
Japan	Chiba Cancer Center ( Site 0005)	Chiba
Japan	Kyushu University Hospital ( Site 0008)	Fukuoka
Japan	National Cancer Center Hospital East ( Site 0002)	Kashiwa	Chiba
Japan	Nagoya University Hospital ( Site 0003)	Nagoya	Aichi
Japan	Okayama University Hospital ( Site 0007)	Okayama
Japan	Kindai University Hospital ( Site 0006)	Osakasayama	Osaka
Japan	Yamagata University Hospital ( Site 0001)	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information