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

Inclusion Criteria

Each prospective participant must meet ALL of the following inclusion criteria in order to be eligible for this study:

* 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

Exclusion Criteria

Potential participants who meet ANY of the following exclusion criteria are not eligible for enrollment into this study:

* Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 5 half-lives or four weeks (whichever is shorter) prior to treatment initiation, or oral therapy within 5 half-lives or one week (whichever is shorter) prior to treatment initiation
* Transformation of follicular lymphoma (FL) to a more aggressive subtype of lymphoma or grade 3b FL
* Participants currently being treated with the following drugs:

  * CYP2C8 substrates with a narrow therapeutic index (such as paclitaxel)
  * P-gp substrates with a narrow therapeutic index (such as digoxin)
  * CYP3A strong inducers (such as rifampin) Note: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment
* Active central nervous system (CNS) involvement
* Pregnant or breast-feeding women
* Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug
* Uncontrolled illness including but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in the past six months, and psychiatric illness that would limit compliance with study requirements
* QT corrected (QTc) prolongation (defined as a QTc \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
* Active Hepatitis B or Hepatitis C infection.
* Other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the participant's safety or interfere with the evaluation of the safety of the study agent
* History of prior cancer within \< 1 year, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas