A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)

Inclusion Criteria

• •Signed written informed consent granted prior to initiation of any study-specific procedures
• •For the dose escalation cohorts, relapsed or refractory (R/R) participants with a diagnosis of B-cell Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and Waldenstrom macroglobulinemia (WM) who have received at least two prior systemic therapies . Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Participants with low grade lymphoma must be progressing and requiring treatment
• •For the expansion cohorts, the following criteria must be met:
• •* Cohort A: R/R CLL/SLL participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented Bruton's tyrosine kinase (BTK) mutation on C481 residue
• •* Cohort B: R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue. In this study, intolerance to standard therapy is defined as having experienced a grade 3 or higher adverse event that was caused by the standard therapy and resulted in treatment discontinuation
• •* Cohort C: Richter's transformation (RT) participants who have failed at least one prior therapy
• •* Cohort D: Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A
• •* Cohort E: Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies
• •* Cohort F: Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies
• •* Cohort G: High-grade B-cell lymphoma participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations
• •* Cohort H: WM participants who have failed at least 2 prior systemic therapies
• •* Cohort I (Food Effect): relapsed or refractory participants with a diagnosis of B-cell NHL, CLL/SLL or WM who have received at least 2 prior systemic therapies, or 1 prior therapy for RT participants. Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Participants with low grade lymphoma must be progressing and requiring treatment.
• •Disease status requirement:
• •* For CLL participanst symptomatic disease that mandates treatment (Hallek et al. 2018)
• •* For B-cell NHL participants, measurable disease by imaging scan
• •* For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal (ULN)
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• •Good organ function
• •Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation or by 24-hour urine collection
• •Total bilirubin ≤ 1.5 x institutional ULN (total bilirubin of ≤ 3 x institutional ULN in participants with documented Gilbert's syndrome)
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN
• •Platelet count ≥ 50,000/µL
• •Absolute neutrophil count (ANC) ≥ 1000/µL
• •Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week.
• •For men and women of child-bearing potential, willing to use adequate contraception (e.g., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study
• •Female participants of child-bearing potential must have a negative serum pregnancy test within 14 days of the first day of drug dosing
• •Ability to swallow oral medications without difficulty