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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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

You cannot join if

• 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

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

nemtabrutinib. An orally available reversible inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, nemtabrutinib non-covalently binds to and inhibits the activity of both the wild-type and the C481S mutated form of BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. Compared to other BTK inhibitors, nemtabrutinib does not require interaction with the BTK C481 site and inhibits the proliferation of cells harboring the BTK C481S mutation. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B lymphocytes. NCI Drug Dictionary

Treatments listed in the registry

• Nemtabrutinib (Drug): Nemtabrutinib tablets administered orally QD.

Na · Single Group · masking: None

Main goals

• Part 1: Number of participants experiencing dose-limiting toxicities (DLTs) (Up to ~56 days (Cycles 1-2, cycle = 28 days))
• Part 1: Number of participants experiencing adverse events (AEs) (Up to ~71 months)
• Part 1: Number of participants discontinuing study treatment due to AEs (Up to ~42 months)
• Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR) (Up to ~61 months)
• Part 2: ORR per Lugano criteria 2014 as assessed by ICR (Up to ~61 months)
• Part 2: ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR (Up to ~71 months)

Other goals

• Part 1: Area Under the Curve (AUC) of Nemtabrutinib
• Part 1: Minimum Concentration (Cmin) of Nemtabrutinib
• Part 1: Maximum Concentration (Cmax) of Nemtabrutinib
• Part 1: ORR per iwCLL criteria 2018 as assessed by ICR
• Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR
• Part 2: Number of participants experiencing AEs
• Part 2: Number of participants discontinuing study treatment due to AEs
• Part 2: AUC of Nemtabrutinib
• Part 2: Cmin of Nemtabrutinib
• Part 2: Cmax of Nemtabrutinib
• Part 2: DOR per iwCLL criteria 2018 as assessed by ICR
• Part 2: DOR per Lugano criteria 2014 as assessed by ICR
• Part 2: DOR per IWWM criteria 2014 as assessed by ICR

Planned enrollment: 490 (estimated).

• Highlands Oncology Group ( Site 2728), Springdale, Arkansas
• University of California San Diego Moores Cancer Center ( Site 2717), La Jolla, California
• Colorado Blood Cancer Institute ( Site 2726), Denver, Colorado
• Astera Cancer Care ( Site 2732), East Brunswick, New Jersey
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704), Hackensack, New Jersey
• UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730), Dallas, Texas
• Medical Oncology Associates (Summit Cancer Centers) ( Site 2710), Spokane, Washington

87 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT04728893
• NCI Drug Dictionary: C138066

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 26, 2026. Public record; not medical advice.