Last updated 2 days ago
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
490 patients around the world
Available in Argentina, Brazil
This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of the 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).
Merck Sharp & Dohme Corp.
10Research sites
490Patients around the world
This study is for people with
Leukemia
Chronic lymphocytic leukemia
Rare diseases
Waldenstrom's macroglobulinemia
Lymphoma
Non-Hodgkin lymphoma
Requirements for the patient
From 18 Years
All Gender
Medical requirements
- 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 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 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.Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2iHas 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 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 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 or bone marrow aspirate (Cohort D) at Screening.Has a 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.
- 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.
Sites
CEMIC - Hospital Universitario Sede Saavedra - CABA, Buenos Aires
Recruiting
Instituto Médico de la Fundación Estudios Clínicos - Rosario
Recruiting
Centro de Internación e Investigación Clínica FUNDALEU
Recruiting
Hospital Alemán
Recruiting
Hospital Privado de Córdoba
Recruiting
Centro Oncológico de Integración Regional C.O.I.R. - Mendoza
Hospital das Clínicas da Faculdade de Medicina da São Paulo - USP
Recruiting
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
Recruiting
Hospital Paulistano
Recruiting
Beneficência Portuguesa de São Paulo
StudyBELLWAVE-003
SponsorMerck Sharp & Dohme Corp.
Study typeInterventional
Conditions
Chronic lymphocytic leukemiaWaldenstrom's macroglobulinemiaNon-Hodgkin lymphoma
Requirements
From 18 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT04728893
