Clinical trial NCT05347225: A Study of Nemtabrutinib (MK-1026) in China Participants With Relapsed or Refractory Hematologic Malignancies (MK-1026-005)
Official title: A Phase 1 Clinical Study to Investigate the Safety, Pharmacokinetics and Efficacy of MK-1026 in China Participants With Relapsed or Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-04-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of oral nemtabrutinib in Chinese participants at least 18 years of age who have Relapsed/Refractory hematologic malignancies.


Eligibility criteria: Inclusion Criteria:

* Relapsed or refractory participants with a diagnosis of B-cell Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) or Waldenström's Macroglobulinemia (WM) who have received no more than 4 prior standard systemic therapies. Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens and those with low grade lymphoma must be progressing and requiring treatment
* Must have received prior systemic treatment before joining this study
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* HBV/HCV viral load undetectable or no history of HBV/HCV
* Has adequate organ function
* Male participants agree to be abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 30 days after the last dose of the study intervention
* Female participant is not a Women of Child Bearing Potential (WOCBP) or is a WOCBP using contraception during the intervention period and for at least 30 days after the last dose of the study intervention

Exclusion Criteria:

* Has a history of prior cancer within \<3 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ, or other in situ carcinomas
* Has active primary tumor involvement of central nervous system (CNS) disease
* Has an active infection requiring systemic therapy
* Has a known history of Human Immunodeficiency Virus (HIV) infection
* Has an uncontrolled illness including but not limited to ongoing symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness
* Had immunotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product ≤4 weeks prior to treatment initiation
* Has any clinically significant gastrointestinal abnormalities that might alter absorption

Primary outcomes:
measure: Number of Participants who Experience Adverse Events (AEs)
timeFrame: Up to ~ 35 months
measure: Number of Participants Discontinuing Study Treatment due to AEs
timeFrame: Up to ~ 35 months
measure: Maximum Concentration (Cmax) of Nemtabrutinib
timeFrame: Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
measure: Minimum Concentration (Cmin) of Nemtabrutinib
timeFrame: Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
measure: Area Under the Plasma Concentration-Time Curve from 0 to 24 Hours (AUC0-24) of Nemtabrutinib
timeFrame: Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
measure: Time to Maximum Concentration (Tmax) of Nemtabrutinib
timeFrame: Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
Secondary outcomes:
measure: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) Criteria 2014 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: ORR per Lugano Criteria 2014 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: DOR per IWWM Criteria 2014 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
measure: DOR per Lugano Criteria 2014 as Assessed by the Investigator
timeFrame: Up to ~ 35 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital-hematology department ( Site 1002)
state: Guangdong
city: Guangzhou
country: China
facility: SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal medicine ( Site 1007)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-hematology department ( Site 1003)
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 1004)
state: Hunan
city: Tianjin
country: China
facility: Institute of hematology&blood disease hospital-Hematology ( Site 1001)
state: Tianjin
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: