Title
A Phase 3 Randomized Study to Compare Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma MK-1026-011 (BELLWAVE-011)

Description
The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per iwCLL Criteria 2018 by BICR.

Objective
Primary Objectives:
- To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to ORR per iwCLL criteria 2018 as assessed by BICR.
- To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to PFS per iwCLL criteria 2018 as assessed by BICR.

Secondary Objectives:
- To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to OS.
- To evaluate DOR per iwCLL criteria 2018 as assessed by BICR.
- To evaluate the safety and tolerability of nemtabrutinib.

Treatment Experimental: Nemtabrutinib
Participants will receive nemtabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.

Active Comparator: Ibrutinib/Acalabrutinib
Participants will receive investigator's choice of ibrutinib or acalabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.

Key Eligibility Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy.

Has at least 1 marker of disease burden.

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.

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 deoxyribonucleic acid (DNA) viral load before randomization.

Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.

Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.

Applicable Disease Sites
Lymphoma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital