ClinicalTrials.gov record NCT04728893
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 2 interventional study evaluates the oral drug nemtabrutinib (MK-1026) in people with various hematologic malignancies. The trial has two parts: a dose escalation/confirmation stage to find the recommended Phase 2 dose, then a cohort expansion stage with disease-specific groups. Participants receive daily oral nemtabrutinib until disease progression or discontinuation while investigators monitor side effects, drug levels, and tumor response.
What it is studying. The study is testing the safety, tolerability, drug levels, and anti-cancer activity of nemtabrutinib (MK-1026) in people with the listed blood cancers. It measures side effects, pharmacokinetics (blood drug levels), and objective tumor response using disease-specific response criteria.
What the researchers hope to learn. To determine the recommended Phase 2 dose of nemtabrutinib, to evaluate its safety profile, to measure drug exposure (pharmacokinetics), and to assess objective response rates and duration of response across the included hematologic malignancies.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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).
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Nemtabrutinib
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
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).
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants take nemtabrutinib tablets by mouth once daily until their disease progresses or they stop treatment. Before and during the study you will have imaging (CT scans) to measure disease and may need a fresh bone‑marrow aspirate or a lymph‑node biopsy for biomarker testing (archival biopsies may be acceptable in some cases). The study requires repeated blood draws—including several samples on early dosing days—to measure drug levels and for safety monitoring, and study staff will record any adverse events. Treatment is organized in 28‑day cycles, with more frequent blood sampling during the early cycles for pharmacokinetic assessments.
How the study is structured. Interventional, single-group, open-label Phase 2 trial in two parts. Part 1 is dose escalation and confirmation to determine the recommended Phase 2 dose (RP2D) and to record early safety and pharmacokinetics. Part 2 is cohort expansion with multiple disease-specific cohorts to assess response and safety. Participants take nemtabrutinib tablets once daily until progressive disease or discontinuation; the study includes blood sampling for drug levels, tumor assessments by standard criteria, and biopsy or bone marrow sampling for biomarker analysis as specified in the protocol.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in Argentina, Australia, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Poland, Romania, South Korea, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Apr 5, 2021
- Primary completion
- Jan 4, 2029 (estimated)
- Study completion
- Jan 4, 2029 (estimated)
- Target enrollment
- 490 participants (estimated)
- Last updated on registry
- Oct 5, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Merck Sharp & Dohme LLC
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Toll Free Number 📞 1-888-577-8839 ✉ Trialsites@msd.com
Participating sites (121)
- Highlands Oncology Group ( Site 2728)Recruiting
Springdale, Arkansas, 72762 · United States
- Study Coordinator · 479-872-8130
- University of California San Diego Moores Cancer Center ( Site 2717)Recruiting
La Jolla, California, 92093-0698 · United States
- Study Coordinator · 858-534-5201
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724)Completed
Torrance, California, 90502 · United States
- Colorado Blood Cancer Institute ( Site 2726)Recruiting
Denver, Colorado, 80218 · United States
- Study Coordinator · 720-754-4800
- The University of Louisville, James Graham Brown Cancer Center ( Site 2729)Completed
Louisville, Kentucky, 40202 · United States
- Mayo Clinic - Rochester ( Site 2706)Active Not Recruiting
Rochester, Minnesota, 55905 · United States
- Astera Cancer Care ( Site 2732)Recruiting
East Brunswick, New Jersey, 08816 · United States
- Study Coordinator · 732-672-6405
- John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704)Recruiting
Hackensack, New Jersey, 07601 · United States
- Study Coordinator · 551-996-3003
- Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708)Completed
Fargo, North Dakota, 58102 · United States
- UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730)Recruiting
Dallas, Texas, 75390 · United States
- Study Coordinator · 972-695-9450
Terms used on this page · explanations by MedicalUpdates.ai
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- randomization
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- prior therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- Cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- relapsed or refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- treatment naive
- Has not previously received the treatment, or the type of treatment, that the study is about.
- relapsed
- A condition that improved with treatment and has since returned or worsened.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- biomarker
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- Computed tomography
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- investigational agent
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- Dose Escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- recommended phase 2 dose
- The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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