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

• Status: Recruiting
• Trial end date: 2027-03-19
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.

Criteria

Inclusion Criteria:

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation

• 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 heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for 12 days after last dose of study intervention

• Female participants not pregnant or breastfeeding are eligible to participate if not a woman of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 30 days after the last dose of study intervention

Part 1 and Part 2 (Cohorts A to C)

• Has a confirmed diagnosis of CLL/SLL

• Has active disease for CLL/SLL clearly documented to initiate therapy

• Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening (optional for participants enrolling in Part 1)

Part 2 (Cohorts D to G)

• Has a confirmed diagnosis of and response to previous treatment of one of the following:

• Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)

• Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTK inhibitor (BTKi) (Cohort E)

• Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)

• Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab), and a phosphoinositide 3-kinase inhibitor (PI3Ki) (Cohort G)

• Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan

• Has an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening

Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi

• Has active disease defined as1 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 ≥4500 g/dL; or bone marrow infiltration of 70%

• Has an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening

Exclusion Criteria:

• Has active HBV/HCV infection (Part 1 and Part 2)

• Has a history of malignancy ≤3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer

• Has active central nervous system (CNS) disease

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection

• Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation

• 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