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).

Launched by MERCK SHARP & DOHME LLC · Jul 7, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study is comparing two treatment combinations: one that includes the medication nemtabrutinib with venetoclax, and another that combines venetoclax with rituximab. The goal is to see if the first combination helps patients live longer without their disease worsening compared to the second combination.

To participate in this trial, patients must have a confirmed diagnosis of CLL or SLL, have tried at least one previous treatment, and have signs of active disease. Eligible patients should be able to take oral medications and have a life expectancy of at least three months. Throughout the study, participants will receive regular check-ups to monitor their health and how well the treatment is working. It’s important to note that certain health conditions or recent treatments might make someone ineligible for this study, so potential participants should discuss their medical history with their doctor.

Gender

ALL

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.