Recruiting

Phase 3

Nemtabrutinib vs. VenetoclaxA 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).

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT05947851

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Chronic Lymphocytic

Small-Cell Lymphoma

Lymphoma, Small Lymphocytic

CLL

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Nemtabrutinib

Venetoclax

Rituximab

Study Details

Brief summary:

The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Chronic Lymphocytic

Small-Cell Lymphoma

Lymphoma, Small Lymphocytic

CLL

Study ID

NCT05947851

Start date

Aug 8, 2023

Status verified date

Aug, 2026

Completion date

Jul 1, 2035

Anticipated

Primary completion date

Jun 1, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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 Criteria:

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

Study Design

Enrollment

735 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Nemtabrutinib + Venetoclax

Participants will receive nemtrabrutinib oral tablets at specified doses daily starting at Cycle 1 Day 1 (C1D1) and venetoclax oral tablets at doses of 20 mg up to 400 mg daily starting at Cycle 2 Day 1 (C2D1) up to 2 years post C2D1 or until progressive disease (PD) or discontinuation. A cycle = 4 weeks.

active comparator: Venetoclax + Rituximab

Participants will receive venetoclax oral tablets at doses from 20 mg up to 400 mg daily starting at C1D1 on 4-week cycles up to 2 years and rituximab or biosimilar at 375 mg/m\^2 up to 500 mg/m2 intravenous infusion once per 28-day cycle starting at C2D1, for 6 total cycles. Treatment will continue until progressive disease (PD) or discontinuation.

Interventions

Nemtabrutinib

5, 20, and 45 tablets

Venetoclax

10, 50, and 100 mg tablets

Rituximab

100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion

Primary outcome measure

Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 12 Weeks ]
Part 1: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 28 months ]
Part 1: Number of Participants Discontinuing Study Treatment Due to AEs [ Time Frame: Up to approximately 25 months ]
Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 71 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839 Trialsites@msd.com

Locations

Highlands Oncology Group ( Site 5405)

Recruiting

Springdale, Arkansas, United States, 72762

Contacts

Study Coordinator

479-872-8130

MemorialCare Health System - Long Beach Medical Center ( Site 5421)

Recruiting

Long Beach, California, United States, 90806

Contacts

Study Coordinator

562-933-7866

Memorial Hospital West ( Site 5410)

Recruiting

Pembroke Pines, Florida, United States, 33028

Contacts

Study Coordinator

954-844-8318

Fort Wayne Medical Oncology and Hematology ( Site 5444)

Recruiting

Fort Wayne, Indiana, United States, 46804

Contacts

Study Coordinator

260-436-0800

Center for Cancer and Blood Disorders ( Site 5439)

Recruiting

Bethesda, Maryland, United States, 20817

Contacts

Study Coordinator

301-571-2016

Hattiesburg Clinic Hematology/Oncology ( Site 5416)

Recruiting

Hattiesburg, Mississippi, United States, 39401

Contacts

Study Coordinator

601-261-1700

MidAmerica Cancer Care, LLC ( Site 5426)

Recruiting

Kansas City, Missouri, United States, 64132

Contacts

Study Coordinator

816-974-5050

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

406-238-6685

Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434)

Recruiting

Reno, Nevada, United States, 89502

Contacts

Study Coordinator

775-982-4000

New York Oncology Hematology, P.C. ( Site 5453)

Recruiting

Albany, New York, United States, 12208

Contacts

Study Coordinator

518-262-6696

Oregon Health and Science University ( Site 5425)

Recruiting

Portland, Oregon, United States, 97239-3011

Contacts

Study Coordinator

503-494-5058

PatientCare Clinical Research LLC ( Site 5435)

Recruiting

Sugar Land, Texas, United States, 77479

Contacts

Study Coordinator

929-712-7467

University of Virginia Cancer Center ( Site 5402)

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

Study Coordinator

434-924-9333

Vista Oncology ( Site 5449)

Recruiting

Olympia, Washington, United States, 98506

Contacts

Study Coordinator

360-413-8880

Medical Oncology Associates, PS ( Site 5406)

Recruiting

Spokane, Washington, United States, 99208

Contacts

Study Coordinator

509-462-2273

The Moncton Hospital ( Site 1414)

Recruiting

Moncton, New Brunswick, Canada, E1C 6Z8

Contacts

Study Coordinator

506-870-2404

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)

Recruiting

Greenfield Park, Quebec, Canada, J4V 2H1

Contacts

Study Coordinator

450-466-5000 x3226

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)

Recruiting

Sherbrooke, Quebec, Canada, J1H 5H4

Contacts

Study Coordinator

819-346-1110 x12811

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-27.