Triple-drug attack aims to wipe out hidden leukemia cells

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patients aged 18 years or older. * Patients must have a diagnosis of CLL/ Small Lymphocytic Lymphoma (SLL) * Patients must meet International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for treatment initiation. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Patient must meet the following screening clinical laboratory values as specified below: * Hematologic: Absolute Neutrophil Count (ANC) of at least 1000 and platelet count of at least 50,000 unless these blood counts are low due to bone marrow involvement by CLL/SLL (use of growth factors, transfusions allowed to meet this criteria as clinically indicated). * International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × Upper Limit of Normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. * Hepatic: i. Total bilirubin ≤1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. Patients with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits and total bilirubin ≤3 x ULN). ii. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN. * Renal: Creatinine clearance of at least 30 mL/min based either on Cockroft-Gault estimate or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or urine collection (12 or 24 hour). * Patient is able to swallow oral medications. * Female subjects who: * Are postmenopausal for at least one year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential: i. Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through six months after the last dose of study drug (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception). iii. Agree to not to donate or freeze egg(s) during the course of this study or within 180 days after receiving their last dose of study drug. * Male subjects, even if surgically sterilized (i.e., status post vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through six months after the last dose of study drug (female and male condoms should not be used together), OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) * Agree to not to donate or freeze sperm during the course of this study or within 180 days after receiving their last dose of study drug. * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable Hepatitis B (HBV) viral load at screening. Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV. * Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization. * Participants with HIV are eligible if they meet ALL of the following criteria: * The CD4 count is \>350 cells/µL at screening * The HIV viral load is below the detectable level as per locally available testing * Are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry i. Note: ART must include drugs which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study). HIV screening tests are not required unless known history of HIV infection \- Ability to understand a written informed consent document, and the willingness to sign it. Exclusion Criteria: \- Active HBV/HCV infection. See inclusion criteria 9 (HBV) and 10 (HCV) for requirements. * Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy). * Diagnosis of Richter Transformation * Active central nervous system (CNS) involvement * Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course. * AIDS defining opportunistic infection in the past 12 months prior to screening. * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. * Clinically significant cardiac issues (unless patient has a pacemaker) such as QTc prolongation (defined as a QTcF \>480 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min) * Known allergy/sensitivity to nemtabrutinib or any of the excipients * History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding. * History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years or no active therapy is needed. NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder. \- A person of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. Prior/Concomitant Therapy * Prior use of any BTKi or Bcl2 inhibitor * Currently being treated with the following drugs: * P-gp substrates with a narrow therapeutic index * CYP3A strong inducers * CYP3A strong inhibitors NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment. * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (if prior therapy was a monoclonal antibody) or 5 half-lives before randomization, whichever is longer. * Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted. \- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Prior/Concurrent Clinical Study Experience * Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited. * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments \- Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications. Note: Biopsy and placement of central venous access devices are not considered major surgery. \- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.