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NCT04728893From ClinicalTrials.govRecruiting

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

A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies

  • Hematologic Malignancies
  • Waldenstroms Macroglobulinaemia
  • Non-Hodgkins Lymphoma
  • Chronic Lymphocytic Leukaemia

At a glance

Phase
Phase 2
Study type
Interventional
Sponsor
Merck Sharp & Dohme LLC
Enrolment target
490
Started
5 April 2021
Main results due
4 January 2029
Study sites
121
Registry updated
24 September 2026

Can you take part?

  • Aged 18 years and over.
  • Open to any sex.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full eligibility criteria
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

What this study is about

In the sponsor’s own words, from the registry.

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).

Study sites(121)

  • Highlands Oncology Group ( Site 2728)

    Springdale, Arkansas, United States

    Recruiting

  • University of California San Diego Moores Cancer Center ( Site 2717)

    La Jolla, California, United States

    Recruiting

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724)

    Torrance, California, United States

    Completed

  • Colorado Blood Cancer Institute ( Site 2726)

    Denver, Colorado, United States

    Recruiting

  • The University of Louisville, James Graham Brown Cancer Center ( Site 2729)

    Louisville, Kentucky, United States

    Completed

  • Mayo Clinic - Rochester ( Site 2706)

    Rochester, Minnesota, United States

    Active, not recruiting

  • Astera Cancer Care ( Site 2732)

    East Brunswick, New Jersey, United States

    Recruiting

  • John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704)

    Hackensack, New Jersey, United States

    Recruiting

  • Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708)

    Fargo, North Dakota, United States

    Completed

  • UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730)

    Dallas, Texas, United States

    Recruiting

  • Medical Oncology Associates (Summit Cancer Centers) ( Site 2710)

    Spokane, Washington, United States

    Recruiting

  • Hospital Aleman ( Site 0102)

    Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

    Recruiting

  • Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)

    Buenos Aires, Buenos Aires F.D., Argentina

    Recruiting

  • Fundacion Estudios Clinicos ( Site 0112)

    Rosario, Santa Fe Province, Argentina

    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, Australia

    Completed

  • Box Hill Hospital ( Site 0203)

    Box Hill, Victoria, Australia

    Recruiting

  • Sir Charles Gairdner Hospital ( Site 0200)

    Nedlands, Western Australia, Australia

    Recruiting

  • Hospital das Clinicas FMUSP-Pesquisa Clínica Hematologia ( Site 0303)

    São Paulo, São Paulo, Brazil

    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, Canada

    Recruiting

  • The Ottawa Hospital ( Site 0404)

    Ottawa, Ontario, Canada

    Recruiting

  • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0406)

    Toronto, Ontario, Canada

    Recruiting

  • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0403)

    Montreal, Quebec, Canada

    Recruiting

  • Jewish General Hospital ( Site 0400)

    Montreal, Quebec, Canada

    Recruiting

  • Anhui Provincial Hospital ( Site 2808)

    Hefei, Anhui, China

    Active, not recruiting

  • Peking University Third Hospital-Hematology ( Site 2827)

    Beijing, Beijing Municipality, China

    Recruiting

  • The Second Affiliated Hospital of Chongqing Medical University ( Site 2825)

    Chongqing, Chongqing Municipality, China

    Active, not recruiting

  • Sun Yat-sen University Cancer Center-Internal Medicine ( Site 2824)

    Guangzhou, Guangdong, China

    Active, not recruiting

  • Liuzhou People's Hospital ( Site 2817)

    Liuzhou, Guangxi, China

    Recruiting

  • Guangxi Medical University Cancer Hospital ( Site 2814)

    Nanning, Guangxi, China

    Recruiting

  • Henan Cancer Hospital-hematology department ( Site 2802)

    Zhengzhou, Henan, China

    Recruiting

  • Wuhan Union Hospital ( Site 2816)

    Wuhan, Hubei, China

    Recruiting

  • The Second Xiangya Hospital of Central South University ( Site 2820)

    Changsha, Hunan, China

    Recruiting

  • Hunan Cancer Hospital ( Site 2822)

    Changsha, Hunan, China

    Recruiting

  • Jiangsu Province Hospital ( Site 2823)

    Nanjing, Jiangsu, China

    Recruiting

  • The Affiliated Hospital of Xuzhou Medical College ( Site 2818)

    Xuzhou, Jiangsu, China

    Completed

  • The First Affiliated Hospital of Nanchang University ( Site 2815)

    Nanchang, Jiangxi, China

    Recruiting

  • The First Hospital of Jilin University-Hematology ( Site 2803)

    Changchun, Jilin, China

    Recruiting

  • Fudan University Shanghai Cancer Center ( Site 2801)

    Shanghai, Shanghai Municipality, China

    Recruiting

  • Huashan Hospital, Fudan University ( Site 2821)

    Shanghai, Shanghai Municipality, China

    Recruiting

  • West China Hospital Sichuan University ( Site 2810)

    Chengdu, Sichuan, China

    Recruiting

  • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Unio ( Site 2800)

    Tianjin, Tianjin Municipality, China

    Recruiting

  • The First Affiliated Hospital, Zhejiang University ( Site 2826)

    Hangzhou, Zhejiang, China

    Recruiting

  • Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0600)

    Brno, Brno-mesto, Czechia

    Recruiting

  • Fakultni nemocnice Hradec Kralove ( Site 0601)

    Hradec Králové, Czechia

    Recruiting

  • Aarhus University Hospital ( Site 0702)

    Aarhus N, Central Jutland, Denmark

    Completed

  • Aalborg Universitetshospital ( Site 0703)

    Aalborg, North Denmark, Denmark

    Recruiting

  • Sjaellands Universitetshospital Roskilde ( Site 0701)

    Roskilde, Region Sjælland, Denmark

    Recruiting

  • Odense University Hospital ( Site 0705)

    Odense C, Region Syddanmark, Denmark

    Completed

  • Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 0810)

    Nice, Alpes-Maritimes, France

    Recruiting

  • Centre Hospitalier Lyon-Sud ( Site 0804)

    Pierre-Bénite, Auvergne-Rhône-Alpes, France

    Recruiting

  • Institut Paoli-Calmettes ( Site 0803)

    Marseille, Bouches-du-Rhone, France

    Recruiting

  • Centre Hospitalier de Versailles ( Site 0809)

    Le Chesnay, Yvelines, France

    Completed

  • Hopital Saint Louis ( Site 0805)

    Paris, France

    Recruiting

  • Universitaetsklinikum Ulm. ( Site 0906)

    Ulm, Baden-Wurttemberg, Germany

    Recruiting

Showing 60 of 121 sites — filter to narrow it down. 95 of the 121 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT04728893. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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