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).

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Chronic Lymphocytic; Small-Cell Lymphoma; Lymphoma, Small Lymphocytic; CLL; SLL

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).


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, immunoglobulin heavy chain gene (ighv) mutation status and bruton's tyrosine kinase (btk)-c481 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 3 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. * has qt interval corrected (qtc) prolongation or other significant electrocardiogram (ecg) abnormalities. * 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) including venetoclax or non-covalent bruton's tyrosine kinase inhibitor (btki). * 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.