Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)

Inclusion Criteria:

• 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 ifthey have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeksand have undetectable HBV viral load prior to randomization

• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable at screening

• Has adequate organ function

• Male participants agree to refrain from donating sperm and agree to either remainabstinent from penile-vaginal intercourse as their preferred and usual lifestyle ORagree to use contraception, during the intervention period and for at least the timerequired to eliminate the study intervention after last dose of study intervention

• Female participants assigned female sex at birth who are not pregnant orbreastfeeding are eligible to participate if not a participant of childbearingpotential (POCBP), or if a POCBP they either use a contraceptive method that ishighly effective OR remain abstinent from penile-vaginal intercourse as theirpreferred and usual lifestyle during the intervention period and for at least toeliminate study intervention after the last dose of study intervention

• Participants with HIV are eligible if they meet all of the following: the CD4 countis >350 cells/uL at screening, the HIV viral load is below the detectable level, areon a stable ART regimen for at least 4 weeks prior to study entry, and are compliantwith their ART

Part 1 and Part 2 (Cohorts A to C and J)

• 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 priortherapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must havereceived and failed, been intolerant to, or determined by their treatingphysician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate orineligible for a PI3Ki per local guidelines

• Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory followingat 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 ofprior therapy

• Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractoryto prior therapy with a covalent/irreversible BTKi and BCL2i

• Has active disease for CLL/SLL clearly documented to initiate therapy

• Has evaluable core or excisional lymph node biopsy for biomarker analysis froman 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 meets the following prior therapy requirements:

• Participants with Richter's transformation who are relapsed or refractoryfollowing at least 1 line of prior therapy (Cohort D)

• Participants with pathologically confirmed MCL, documented by eitheroverexpression of cyclin D1 or t(11;14), who are relapsed or are refractory tochemoimmunotherapy and a covalent irreversible BTKi (Cohort E)

• Participants with MZL (including splenic, nodal, and extra nodal MZL) who arerelapsed 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 measuredin at least 2 dimensions with spiral CT scan

• Has a lymph node biopsy for biomarker analysis from an archival or newly obtainedbiopsy or bone marrow aspirate (Cohort D) 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, physicalfindings, laboratory abnormalities, coexisting disease

• Has measurable disease, satisfying any of the following: at least 1 lesion that canbe accurately measured in at least 2 dimensions with spiral CT scan (minimummeasurement 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 atScreening or a lymph node biopsy from an archival

Exclusion Criteria:

• 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, orcarcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that haveundergone 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 surveillancewith 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 investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention

• Has any clinically significant gastrointestinal abnormalities that might alterabsorption

• History of severe bleeding disorders