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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).

NCT05947851 · Merck Sharp & Dohme LLC
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Official title
A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)
About this study
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).
Eligibility criteria
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 target: 735 participants
Allocation: randomized
Masking: single
Age groups: adult, older_adult
Timeline
Starts: 2023-08-08
Estimated completion: 2035-07-01
Last updated: 2026-05-18
Interventions
Drug: NemtabrutinibDrug: VenetoclaxBiological: Rituximab
Primary outcomes
  • Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) (Up to approximately 12 Weeks)
  • Part 1: Number of Participants Experiencing Adverse Events (AEs) (Up to approximately 28 months)
  • Part 1: Number of Participants Discontinuing Study Treatment Due to AEs (Up to approximately 25 months)
Sponsor
Merck Sharp & Dohme LLC · industry
Contacts & investigators
ContactToll Free Number · contact · Trialsites@msd.com · 1-888-577-8839
InvestigatorMedical Director · study_director, Merck Sharp & Dohme LLC
All locations (54)
Highlands Oncology Group ( Site 5405)Recruiting
Springdale, Arkansas, United States
MemorialCare Health System - Long Beach Medical Center ( Site 5421)Recruiting
Long Beach, California, United States
Memorial Hospital West ( Site 5410)Recruiting
Pembroke Pines, Florida, United States
Oregon Health and Science University ( Site 5425)Recruiting
Portland, Oregon, United States
Medical Oncology Associates, PS ( Site 5406)Recruiting
Spokane, Washington, United States
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)Completed
Madison, Wisconsin, United States
Instituto Alexander Fleming ( Site 1005)Recruiting
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)Recruiting
Mar del Plata, Buenos Aires, Argentina
Sanatorio Parque ( Site 1003)Recruiting
Rosario, Santa Fe Province, Argentina
Centro Medico Fleischer ( Site 1006)Recruiting
Buenos Aires, Argentina
Hospital Aleman-oncohematologic diseases ( Site 1001)Recruiting
Buenos Aires, Argentina
Royal Adelaide Hospital ( Site 1104)Recruiting
Adelaide, South Australia, Australia
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)Recruiting
Melbourne, Victoria, Australia
UZ Leuven-Hematology ( Site 1200)Recruiting
Leuven, Vlaams-Brabant, Belgium
ZAS Cadix ( Site 1203)Recruiting
Antwerp, Belgium
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)Active Not Recruiting
São Paulo, Brazil
The Moncton Hospital ( Site 1414)Recruiting
Moncton, New Brunswick, Canada
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)Recruiting
Greenfield Park, Quebec, Canada
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 1410)Recruiting
Sherbrooke, Quebec, Canada
Biocenter ( Site 1507)Recruiting
Concepción, Biobio, Chile
IC La Serena Research ( Site 1506)Recruiting
La Serena, Coquimbo Region, Chile
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)Recruiting
Santiago, Region M. de Santiago, Chile
FALP-UIDO ( Site 1500)Recruiting
Santiago, Region M. de Santiago, Chile
Clínica Inmunocel ( Site 1511)Recruiting
Santiago, Region M. de Santiago, Chile
Fundación Valle del Lili ( Site 1703)Recruiting
Cali, Valle del Cauca Department, Colombia
Hopital Claude Huriez - CHU de Lille ( Site 2107)Recruiting
Lille, Nord, France
Centre Hospitalier Universitaire Estaing ( Site 2105)Recruiting
Clermont-Ferrand, Puy-de-Dome, France
CHD Vendee ( Site 2100)Recruiting
La Roche-sur-Yon, Vendee, France
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)Recruiting
Trier, Rhineland-Palatinate, Germany
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)Recruiting
Leipzig, Saxony, Germany
Rambam Health Care Campus ( Site 2801)Recruiting
Haifa, Israel
Hadassah Medical Center-Hemato-Oncology ( Site 2812)Recruiting
Jerusalem, Israel
Sheba Medical Center-Hemato Oncology ( Site 2809)Recruiting
Ramat Gan, Israel
Sourasky Medical Center ( Site 2811)Recruiting
Tel Aviv, Israel
Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2906)Recruiting
Alessandria, Italy
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)Recruiting
Milan, Italy
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)Recruiting
Reggio Emilia, Italy
Centro de Infusion Superare ( Site 3314)Recruiting
Mexico City, Mexico City, Mexico
Health Pharma Professional Research S.A. de C.V: ( Site 3301)Recruiting
Mexico City, Mexico City, Mexico
Centro de Investigacion Clinica Chapultepec ( Site 3309)Recruiting
Morelia, Michoacán, Mexico
Auxilio Mutuo Cancer Center ( Site 3900)Recruiting
San Juan, Puerto Rico
Alberts Cellular Therapy. ( Site 4401)Recruiting
Pretoria, Gauteng, South Africa
Groote Schuur Hospital ( Site 4400)Recruiting
Cape Town, Western Cape, South Africa
Haemalife ( Site 4407)Recruiting
Kuilsriver, Western Cape, South Africa
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)Recruiting
L'Hospitalet Del Llobregat, Barcelona, Spain
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)Recruiting
Pozuelo de Alarcón, Madrid, Spain
HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)Recruiting
Valencia, Valenciana, Comunitat, Spain
Ege Universitesi Hastanesi ( Site 4902)Recruiting
Bornova, İzmir, Turkey (Türkiye)
Namik Kemal University Medical Faculty-Hematology ( Site 4912)Recruiting
Tekirdağ, Tekirdas, Turkey (Türkiye)
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)Completed
Ankara, Turkey (Türkiye)
Mega Medipol-Hematology ( Site 4904)Recruiting
Istanbul, Turkey (Türkiye)
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906)Recruiting
Istanbul, Turkey (Türkiye)
City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)Recruiting
Nottingham, England, United Kingdom
University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)Recruiting
London-Camden, London, City of, United Kingdom
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). · TrialPath