Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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).

Official Title

A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies

Details

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).

Keywords

Hematologic Malignancies, Neoplasms, Hematologic Neoplasms, Nemtabrutinib

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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
  • Participants with 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)

  • Has a confirmed diagnosis of 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
  • 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 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) (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 a 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 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 CAN'T 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 (eg, 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 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
  • History of severe bleeding disorders

Locations

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site accepting new patients
    Torrance California 90502 United States
  • Medical Oncology Associates (Summit Cancer Centers) ( Site 2710) accepting new patients
    Spokane Washington 99208 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Merck Sharp & Dohme LLC
Links
Merck Oncology Clinical Trials Information
ID
NCT04728893
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 450 study participants
Last Updated