RecruitingPhase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how safe nemtabrutinib is and how well it works. It is for people with certain blood cancers, including CLL/SLL, Richter's transformation, several types of lymphoma, and Waldenström's macroglobulinemia.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have one of the listed blood cancers and meet your study group's past treatment rules. Most groups require cancer that came back or did not respond to treatment.
  • Meet your group's rules for active or measurable cancer and provide any required lymph node or bone marrow samples.
  • Be able to care for yourself and be out of bed or a chair for at least half of your waking hours, as checked within 7 days before treatment.
  • Be expected to live at least 3 months, have organs that work well enough, and be able to swallow and keep down medicine.
  • If you have hepatitis B, have at least 4 weeks of antiviral treatment and no virus detected before group assignment. If you had hepatitis C, no virus can be detected at screening.
  • If you have HIV, have a CD4 immune cell count above 350 and no virus detected at screening. You must have followed a stable HIV treatment plan for at least 4 weeks.
  • Men must not donate sperm and must use birth control or avoid penis-in-vagina sex as their usual lifestyle during treatment and until the study drug has cleared afterward.
  • People assigned female at birth must not be pregnant or breastfeeding. Those who can become pregnant must use highly effective birth control or avoid penis-in-vagina sex as their usual lifestyle during treatment and until the drug has cleared afterward.

Who can't join

  • Have active hepatitis B or hepatitis C.
  • Have had another cancer within the past 3 years. Exceptions include certain treated skin cancers, treated cancers that have not spread beyond where they started, and certain low-risk prostate cancers.
  • Have active disease in the brain or spinal cord.
  • Have an active infection that needs treatment throughout the body.
  • Recently received cancer treatment that works throughout the body. The waiting period depends on the drug; it is 4 weeks for monoclonal antibodies.
  • Used an experimental drug or device in another study within 4 weeks before the first study dose.
  • Have a major stomach or bowel problem that could affect how your body takes in the drug.
  • Have a history of severe bleeding disorders.

Simplified for readability. The official criteria below are what the study team uses.

Official 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

Study sites (11)

AR

CA

  • University of California San Diego Moores Cancer Center ( Site 2717) · La Jolla, CA 92093-0698Study Coordinator · Study contact · 858-534-5201More trials in La Jolla
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724) · Torrance, CA 90502More trials in Torrance

CO

KY

MN

ND

  • Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708) · Fargo, ND 58102More trials in Fargo

NJ

TX

WA