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Clinical Trials in the USA / NCT04728893
Recruiting Phase 2

Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)

NCT04728893 · tracked via the Priya Life Science USA tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 2
Started
2021-04-05
Last updated
2026-08-21

Condition(s) studied

Hematologic MalignanciesWaldenstroms MacroglobulinaemiaNon-Hodgkins LymphomaChronic Lymphocytic Leukaemia

Investigational drug(s) / intervention(s)

Nemtabrutinib

Nemtabrutinib: Nemtabrutinib tablets administered orally QD.

Study summary

The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before C1D1 (the first dose of study treatment) * Has a life expectancy of at least 3 months, based on the investigator assessment * Has the ability to swallow and retain oral medication * Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization * Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Has adequate organ function * Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention * Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention * Participants with Human immunodeficiency virus (HIV) are eligible if they meet all of the following: the CD4 count is \>350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART Part 1 and Part 2 (Cohorts A to C and J) * Has a confirmed diagnosis of Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) with * At least 2 lines of prior therapy (Part 1 only) * Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines * Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive * Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy * Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i. NOTE: As of Protocol Amendment 09, at least 10 CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi, BCL2i and noncovalent/reversible BTKi (all three classes of therapies are required) will be enrolled into Cohort J * Has active disease for CLL/SLL clearly documented to initiate therapy * For SLL participants in Part 2: Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1) Part 2 (Cohorts D to G) \- Has a confirmed diagnosis of and meets the following prior therapy requirements: * Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D) * Participants with pathologically confirmed Mantle-cell lymphoma (MCL), documented by either overexpression of cyclin D1 or t (11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E) * Participants with Marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to at least one prior line of systemic therapy including an anti-CD20-based regimen * Participants with Follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy and immunomodulatory agents (such as lenalidomide based regimen) (Cohort G) * Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral Computed tomography (CT) scan * Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening Part 2 (Cohort H): confirmed diagnosis of Waldenström's macroglobulinemia (WM); participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi * Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease * Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be \>15 mm in the longest diameter or \>10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10% * Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival Exclusion Criteria: * Has active HBV/HCV infection (Part 1 and Part 2) * Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded * Has active central nervous system (CNS) disease * Has an active infection requiring systemic therapy * Has received prior systemic anti-cancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before C1D1 * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention * Has any clinically significant gastrointestinal abnormalities that might alter absorption * History of severe bleeding disorders

Primary outcome measure(s)

Trial sites (121)

FacilityCityRegionStatus
Highlands Oncology Group ( Site 2728) Springdale Arkansas Recruiting
University of California San Diego Moores Cancer Center ( Site 2717) La Jolla California Recruiting
Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724) Torrance California Completed
Colorado Blood Cancer Institute ( Site 2726) Denver Colorado Recruiting
The University of Louisville, James Graham Brown Cancer Center ( Site 2729) Louisville Kentucky Completed
Mayo Clinic - Rochester ( Site 2706) Rochester Minnesota Active Not Recruiting
Astera Cancer Care ( Site 2732) East Brunswick New Jersey Recruiting
John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704) Hackensack New Jersey Recruiting
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708) Fargo North Dakota Completed
UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730) Dallas Texas Recruiting
Medical Oncology Associates (Summit Cancer Centers) ( Site 2710) Spokane Washington Recruiting
Hospital Aleman ( Site 0102) Ciudad Autonoma de Buenos Aires Buenos Aires Recruiting
Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103) Buenos Aires Buenos Aires F.D. Recruiting
Fundacion Estudios Clinicos ( Site 0112) Rosario Santa Fe Province Recruiting
FUNDALEU ( Site 0104) Caba Argentina Recruiting
Hospital Privado Universitario de Córdoba ( Site 0107) Córdoba Argentina Recruiting
Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0110) Mendoza Argentina Completed
Nepean Hospital-Nepean Cancer Care Centre ( Site 0204) Sydney New South Wales Completed
Box Hill Hospital ( Site 0203) Box Hill Victoria Recruiting
Sir Charles Gairdner Hospital ( Site 0200) Nedlands Western Australia Recruiting
Hospital das Clinicas FMUSP-Pesquisa Clínica Hematologia ( Site 0303) São Paulo São Paulo Recruiting
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0300) Rio de Janeiro Brazil Recruiting
BP - A Beneficencia Portuguesa de São Paulo ( Site 0302) São Paulo Brazil Active Not Recruiting
Hospital Paulistano - Amil Clinical Research ( Site 0311) São Paulo Brazil Recruiting
Arthur J.E. Child Comprehensive Cancer Centre ( Site 0401) Calgary Alberta Recruiting
The Ottawa Hospital ( Site 0404) Ottawa Ontario Recruiting
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0406) Toronto Ontario Recruiting
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0403) Montreal Quebec Recruiting
Jewish General Hospital ( Site 0400) Montreal Quebec Recruiting
Anhui Provincial Hospital ( Site 2808) Hefei Anhui Active Not Recruiting
Peking University Third Hospital-Hematology ( Site 2827) Beijing Beijing Municipality Recruiting
The Second Affiliated Hospital of Chongqing Medical University ( Site 2825) Chongqing Chongqing Municipality Active Not Recruiting
Sun Yat-sen University Cancer Center-Internal Medicine ( Site 2824) Guangzhou Guangdong Active Not Recruiting
Liuzhou People's Hospital ( Site 2817) Liuzhou Guangxi Recruiting
Guangxi Medical University Cancer Hospital ( Site 2814) Nanning Guangxi Recruiting
Henan Cancer Hospital-hematology department ( Site 2802) Zhengzhou Henan Recruiting
Wuhan Union Hospital ( Site 2816) Wuhan Hubei Recruiting
The Second Xiangya Hospital of Central South University ( Site 2820) Changsha Hunan Recruiting
Hunan Cancer Hospital ( Site 2822) Changsha Hunan Recruiting
Jiangsu Province Hospital ( Site 2823) Nanjing Jiangsu Recruiting

+ 81 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04728893 on ClinicalTrials.gov ↗ ← All trials in the USA