Brief Summary
The purpose of this study is to assess the safety and tolerability and to confirm the dosethe amount of medication taken 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 Chronica long-lasting disease that changes slowly over time Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).
Intervention / Treatment
- Drug: Nemtabrutinib
- Drug: Venetoclax
- Biological: Rituximab
Inclusion Criteria
- Confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of chronic lymphocytic leukemia/small lymphocytic lymphomacancers of the lymphatic system (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 Oncologythe study, diagnosis and treatment of cancer 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) infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer 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.