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

  • STATUS
    Recruiting
  • End date
    Mar 19, 2027
  • participants needed
    400
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 1 December 2021
chronic lymphocytic leukemia
lymphoma
measurable disease
leukemia
kinase inhibitor
hepatitis b surface antigen
mantle cell lymphoma

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 Waldenstrm's macroglobulinemia (WM).

Description

This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of a 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).

Details
Condition Hematologic Malignancy, Blood disorder, Blood Cancer, Hematologic Cancer, Hematological Disorders, Hematologic Neoplasms, hematological malignancy, hematologic malignancies, hematological tumor, haematological malignancy, hematological malignancies
Treatment MK-1026, Nemtabrutinib
Clinical Study IdentifierNCT04728893
SponsorMerck Sharp & Dohme Corp.
Last Modified on1 December 2021

Eligibility

Yes No Not Sure

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
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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