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Looking for participantsPhase2

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

Sponsor: Merck Sharp & Dohme LLC

NCT ID: NCT04728893

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Nemtabrutinib (drug)
How long the study runs
Study runs about 93 months (dates as stated)
About the drug or intervention
Nemtabrutinib — drug: Nemtabrutinib tablets administered orally QD.
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
490
Started
2021-04-05
Last checked
2026-10

Plain English Summary

What is this study?

  • • Testing a new treatment for hematologic malignancies
  • • Phase2 - 490 participants
  • • 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)

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with hematologic malignancies

Where?

  • • Bristol - Bristol Haematology and Oncology Centre ( Site 2610)
  • • Nottingham - Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 2601)
  • • Windsor - GenesisCare - Windsor ( Site 2608)
  • • London - Sarah Cannon Research Institute UK ( Site 2612)
  • • +4 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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).

More detail

This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of the recommended phase 2 dose (RP2D) in Part 1, the study plans to proceed with Part 2 using 8 disease-specific expansion cohorts (Cohorts A to H).

Hematologic MalignanciesWaldenstroms MacroglobulinaemiaNon-Hodgkins LymphomaChronic Lymphocytic Leukaemia

How this trial compares with your answers

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What we know so far

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Biomarkers mentioned

CD4TP53CD20

Treatment history

Treatments you must have had:

  • ✓ to eliminate the study intervention after last dose of study intervention
  • ✓ (Part 1 only)
  • ✓ a covalent
  • ✓ and are BTKi treatment naive

What the study is looking for

  • ✓Has an activity scale (ECOG) performance status of 0 to 2 within 7 days before C1D1 (the first...
  • ✓Has a expected to live at least 3 $2, based on the investigator assessment
  • ✓Has the ability to swallow and retain oral medication
  • ✓Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at...
  • ✓Has healthy organ

Who cannot take part

  • ✗Has active HBV/HCV infection (Part 1 and Part 2)
  • ✗Has active central nervous system (CNS) disease
  • ✗Has an active infection requiring treatment that goes through your whole body
  • ✗Has received prior systemic anti-cancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal...
  • ✗Is currently participating in or has participated in a study of an investigational agent or has used an...
See the full 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

Where Is This Study? (8 UK sites)

Bristol Haematology and Oncology Centre ( Site 2610)

Bristol BS2 8ED, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01173426733

Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 2601)

Nottingham NG5 1PF, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441159691169

GenesisCare - Windsor ( Site 2608)

Windsor SL4 3HD, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+447989474250

Sarah Cannon Research Institute UK ( Site 2612)

London W1G 6AD, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator02032195234

GenesisCare - Oxford ( Site 2607)

Oxford OX4 6LB, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+447989474250

GenesisCare - Cambridge ( Site 2611)

Newmarket CB8 7XN, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01223 655145

The Royal Marsden NHS Foundation Trust. ( Site 2606)

Sutton SM2 5PT, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator020 8642 6011

The Christie NHS Foundation Trust ( Site 2602)

Manchester M20 4BX, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01619561217

How to Get in Touch

Toll Free Number

Sponsor contact

CONTACT

1-888-577-8839 Trialsites@msd.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-10