Study of Nemtabrutinib Plus Venetoclax for CLL/SLL

This study is looking at a new combination of medicines, nemtabrutinib and venetoclax, for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has come back or not responded to previous treatments. It compares this new combination to a standard treatment of venetoclax plus rituximab. The main goal is to see if the nemtabrutinib and venetoclax combination is better at preventing the disease from getting worse. Researchers will also check for side effects and find the right dose of nemtabrutinib. You may be eligible if you have CLL/SLL that has relapsed or is refractory, and your doctors will need to check for specific genetic markers like TP53 mutations. The study plans to enroll about 735 participants, but its current status is unclear.

Study design
This is an interventional study planning to enroll about 735 participants. It compares two different drug combinations for CLL/SLL.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Participants will be monitored for adverse events for up to approximately 28 months, and for discontinuing treatment due to adverse events for up to approximately 25 months.

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NCT05947851

A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).

Recruiting
PHASE3Ages 18+InterventionalTreatment
Merck Sharp & Dohme LLC
~735 participants
Updated 2026-08-27 on ClinicalTrials.gov
What's tested:NemtabrutinibVenetoclaxRituximab

At a glance

Recruiting sites
62 of 65 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Measured over Up to approximately 12 Weeks
+3 more outcomes measured
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Chronic Lymphocytic
Small-Cell Lymphoma
Lymphoma, Small Lymphocytic
CLL
SLL
65 sites across 50 states
Israel4
Region M. de Santiago3
Italy3
Turkey (Türkiye)3
Washington2
Buenos Aires2
Argentina2
Quebec2
  • Medical Director · STUDY_DIRECTOR · Merck Sharp & Dohme LLC

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Eligibility criteria

Inclusion

Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy
Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, and immunoglobulin heavy chain gene (IGHV) mutation status results required before randomization for Part 2 participants only
Relapsed or refractory to at least 1 prior available therapy
Have 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 a life expectancy of at least 3 months
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
Participants with adequate organ function with specimens collected within 7 days before the start of study intervention
If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception
Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding

Exclusion

Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection
Has gastrointestinal (GI) dysfunction that may affect drug absorption
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL
Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening
HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening
Clinically significant cardiovascular disease
Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients
Has history of severe bleeding disorders (eg, hemophilia)
Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization
Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) within ≤ 12 months before randomization or has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids
Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Participants who have not adequately recovered from major surgery or have ongoing surgical complications
  • Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)Up to approximately 12 Weeks

    DLT evaluation period is defined as 8 weeks after the first dose of the combination treatment of nemtabrutinib plus venetoclax Cycle 2 Day 1 in Part 1 + 4 weeks follow up. Each cycle is 4 weeks. DLTs are: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting \>7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib or venetoclax doses as a result of drug-related adverse events during the first 2 cycles; Grade 5 toxicity.

  • Part 1: Number of Participants Experiencing Adverse Events (AEs)Up to approximately 28 months

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1.

  • Part 1: Number of Participants Discontinuing Study Treatment Due to AEsUp to approximately 25 months

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported for Part 1.

  • Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Blinded Independent Central Review (BICR)Up to approximately 71 months

    PFS is defined as the time from randomization to the first documented disease progression per iwCLL criteria 2018 as accessed by BICR, or death due to any cause, whichever occurs first. PFS will be presented.