A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants with Hematologic Malignancies
- Conditions
- Chronic lymphocytic leukemia/Small lymphocytic lymphomaRichters transformationMantle cell lymphoma, Marginal zone lymphomaFollicular lymphomaWaldenström’s macroglobulinemiaMedDRA version: 21.1Level: LLTClassification code: 10066481Term: Hematological malignancy Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-504931-42-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 502
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation, Part 1 and Part 2 (Cohorts A to C) Has a confirmed diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (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 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 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 chemoimmunotherapy and a covalent irreversible BTKi (Cohort F) Participants with follicular lymphoma (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 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); immunoglobulin M (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 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
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 stable disease (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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method