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RecruitingInterventionalPhase 3

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

NCT ID: NCT06136559Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-12

Summary

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.

Arms & interventions

  • DrugNemtabrutinib

    Administered orally

  • DrugIbrutinib

    Administered orally

  • DrugAcalabrutinib

    Administered orally

Outcome measures

Primary

  • 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 ~33 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 ~104 months

Secondary

  • Overall Survival (OS)

    Time frame: Up to ~104 months

  • Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR

    Time frame: Up to ~104 months

  • Number of Participants Who Experience One or More Adverse Events (AEs)

    Time frame: Up to ~104 months

  • Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: Up to ~104 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection. * Has gastrointestinal (GI) dysfunction that may affect drug absorption. * Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL. * Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening. * Has clinically significant cardiovascular disease. * Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients. * Has history of severe bleeding disorder. * Has known additional malignancy that is progressing or has required active treatment within the past 2 years. * Has received any systemic anticancer therapy for CLL/SLL. * 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. * Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids. * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. * Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration. * Has active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening. * Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Study locations (43)

USA Mitchell Cancer Institute ( Site 0014)

Mobile, Alabama, 36604

Recruiting
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Banner MD Anderson Cancer Center ( Site 0059)

Gilbert, Arizona, 85234

Recruiting
Study Coordinator · Contact

Banner MD Anderson Cancer Center - University Medical Center Phoenix ( Site 0051)

Phoenix, Arizona, 85006

Recruiting
Study Coordinator · Contact

Arizona Oncology Associates - NAHOA ( Site 8007)

Prescott, Arizona, 86301

Completed

Alta Bates Summit Medical Center ( Site 0004)

Berkeley, California, 94704

Recruiting
Study Coordinator · Contact

Moores Cancer Center ( Site 0003)

La Jolla, California, 92093-0698

Recruiting
Study Coordinator · Contact

Care Access - South Pasadena ( Site 0070)

Pasadena, California, 91105

Recruiting
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Saint Joseph Hospital ( Site 0026)

Denver, Colorado, 80218

Recruiting
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Lutheran Medical Center ( Site 0027)

Golden, Colorado, 80401

Recruiting
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Intermountain Health St. Mary's Regional Hospital ( Site 0025)

Grand Junction, Colorado, 81501

Recruiting
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Eastern CT Hematology & Oncology Associates ( Site 0033)

Norwich, Connecticut, 06360

Recruiting
Study Coordinator · Contact

Clermont Oncology Center ( Site 0046)

Clermont, Florida, 34711

Recruiting
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Florida Cancer Specialists - South ( Site 7001)

Fort Myers, Florida, 33901

Recruiting
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Florida Cancer Specialists - East ( Site 7002)

West Palm Beach, Florida, 33401

Recruiting
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Parkview Research Center at Parkview Regional Medical Center ( Site 0002)

Fort Wayne, Indiana, 46845

Recruiting
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University of Iowa Health Care. ( Site 0017)

Waukee, Iowa, 50263

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University of Iowa Health Care. ( Site 0057)

Waukee, Iowa, 50263

Recruiting
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Saint Elizabeth Healthcare ( Site 0041)

Edgewood, Kentucky, 41017

Recruiting
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Corewell Health-Lemmon Holton Cancer Pavilion ( Site 0011)

Grand Rapids, Michigan, 49503

Recruiting
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Regions Hospital ( Site 0042)

Saint Louis Park, Minnesota, 55416

Recruiting
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MidAmerica Cancer Care, LLC ( Site 0043)

Kansas City, Missouri, 64132

Recruiting
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Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0052)

Billings, Montana, 59102

Recruiting
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Summit Medical Group Cancer Center ( Site 0007)

Florham Park, New Jersey, 07932

Completed

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0016)

Hackensack, New Jersey, 07601

Recruiting
Study Coordinator · Contact

New York Oncology Hematology, P.C. ( Site 0069)

Albany, New York, 12208

Recruiting
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Roswell Park Cancer Institute ( Site 0023)

Buffalo, New York, 14263

Recruiting
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RPCI Oncology, PC- Northtowns ( Site 0061)

Williamsville, New York, 14221

Recruiting
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Carolina Oncology Specialists, PA ( Site 0054)

Charlotte, North Carolina, 28207

Recruiting
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Southeastern Medical Oncology Center ( Site 0049)

Goldsboro, North Carolina, 27534

Recruiting
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Consultants in Medical Oncology and Hematology (CMOH) ( Site 8002)

Broomall, Pennsylvania, 19008

Recruiting
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Cancer Care Associates Of York ( Site 0005)

York, Pennsylvania, 17403

Recruiting
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Tennessee Oncology-Chattanooga ( Site 0045)

Chattanooga, Tennessee, 37404

Recruiting
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Tennessee Oncology, PLLC - Elliston Place Plaza Medical Oncology & Hematology ( Site 0031)

Nashville, Tennessee, 37203

Recruiting
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Texas Oncology - Central/South Texas ( Site 8008)

Austin, Texas, 78705

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The Center for Cancer and Blood Disorders ( Site 0032)

Fort Worth, Texas, 76104

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Texas Oncology - San Antonio ( Site 8006)

San Antonio, Texas, 78217

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Texas Oncology - Northeast Texas ( Site 8012)

Tyler, Texas, 75702

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University of Virginia Cancer Center ( Site 0040)

Charlottesville, Virginia, 22903

Recruiting
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Inova Schar Cancer Institute ( Site 0015)

Fairfax, Virginia, 22031

Recruiting
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Virginia Commonwealth University (VCU) Medical Center ( Site 0030)

Richmond, Virginia, 23298

Recruiting
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Medical Oncology Associates, PS (dba Summit Cancer Centers) ( Site 0010)

Spokane, Washington, 99208

Recruiting
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SSM Health Dean Medical Group - South Madison Campus Health Research/Circuit Clinical ( Site 0048)

Madison, Wisconsin, 53715

Recruiting
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University Hospital and UW Health Clinics ( Site 0006)

Madison, Wisconsin, 53792

Recruiting
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