A Phase 3 interventional study of Nemtabrutinib and Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, sponsored by Merck Sharp & Dohme LLC. Recruiting at 203 sites in 29 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment
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.
The main inclusion criteria include but are not limited to the following:
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
Participants will receive nemtabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.
Drug: Nemtabrutinib
Participants will receive investigator's choice of ibrutinib or acalabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.
Drug: Ibrutinib · Drug: Acalabrutinib
Administered orally
Also known as: MK-1026, ARQ 531
Administered orally
Administered orally
Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR)
ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or partial response (PR), per iwCLL Criteria 2018 as assessed by BICR.
Time frame: Up to approximately 44 months
Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD is evaluated per iwCLL Criteria 2018 as assessed by BICR.
Time frame: Up to approximately 104 months
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 104 months
Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR
For participants who demonstrate a complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or partial response (PR) per iwCLL Criteria 2018 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR, CRi, nPR, or PR that led to response until disease progression or death due to any cause, whichever occurs first.
Time frame: Up to approximately 104 months
Number of Participants Who Experience One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to approximately 104 months
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to approximately 104 months
Showing the first 100 of 203 sites across 29 countries.
Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Leukemia, Lymphocytic, Chronic, B-Cell→
Merck Sharp & Dohme LLC