A Phase 2 Study of Epcoritamab as a Consolidation Therapy for 2nd Generation BTKi +/- Obinutuzumab in CLL/SLL Patients or Variants of This.

Inclusion Criteria 1. Diagnosis of CLL or SLL meeting the established 2018 iwCLL diagnostic criteria or variant of CLL/SLL and has received a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab for a minimum of 12 months as first line therapy. a) Note: Variation in flow cytometry is defined as patients who have atypical immunophenotyping for CLL (CD5 negative, CD23 negative or surface expression of CD79b that is bright ) but clinically behave like CLL (leukocytosis, lymphadenopathy and splenomegaly) and have the FISH/Cytogenetics translocations(del 13q, trisomy 12, Del11q) or genomic features (XPO1, NOTCH1, SF3B1, FBXW7, MYD88, BIRC3, TRAF3, NFKBIE, SAMHD1, POT1, HIST1H1E, CHD2, ZMYM3, EGR2 and others) that are suggestive of CLL. 2. Attainment of Partial Response or greater with a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab but detectable disease in blood or bone marrow by NGS ClonoSEQ. 3. Age ≥18 years. 4. ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix D). 5. Patients must have adequate organ and marrow function as defined below: Absolute neutrophil count ≥1,000/mcL, unless if neutropenia is due to underlying CLL bone marrow disease. Hemoglobin ≥8 g/dl unless if related to underlying CLL Platelets ≥50,000/ µL unless if related to underlying CLL Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (excepting Gilbert's syndrome, who may have a bilirubin \> 1.5 × ULN, per discussion between the Investigator and the UC PI). AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Glomerular filtration rate (GFR) Calculated GFR using CKD-EPI formula ≥ 30 (See Appendix E) or multiplying the estimate of GFR by an individual body surface area calculated using an appropriate formula and dividing by 1.73 m2. 6. Women of childbearing potential and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 4 months after discontinuing study drug: 1. Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable. 2. Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. 3. Intrauterine device. 4. Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 1-month prior to study drug administration. 7. Women of childbearing potential must have a negative pregnancy result as follows: At Screening on a serum sample obtained within 7 days prior to the first study drug administration. If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation. 8. Non-sterile males must refrain from sperm donation, from initial study drug administration until 4 months after the last dose of study drug. 9. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. Exclusion Criteria: 1. Obtaining a CR or nodal PR with no detectable disease in blood or bone marrow after treatment with a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab as assessed by Adaptive's NGS ClonoSEQ. 2. Absence of CD20 expression on CLL cells at pre-treatment. 3. Received any prior treatment ever with a CD3×CD20 bispecific antibody. 4. Organ transplant recipients are excluded except those with no active graft versus host disease (GVHD) requiring treatment within 12 months of beginning treatment on study. 5. Receipt of a live vaccine within 28 days prior to study treatment initiation. 6. Autoimmune diseases requiring high dose immunosuppressives (e.g., above 20 mg prednisone daily). 7. Central nervous system (CNS) disease(s) unless in the opinion of the investigator these would not preclude the patient from participation. 8. Known hypersensitivity to any of the components of the treatment drugs (see Investigators Brochure for a list of components). 9. Patients with active Richter's transformation. a. Note: the following will be eligible and not excluded: patients with accelerated phase or prolymphocytic progression 10. Patients who have received prior radiation therapy (RT) unless in the opinion of the investigator the prior receipt of RT will not adversely impact the patient's ability to participate. 11. Patients who require anti-coagulation with warfarin or equivalent Vitamin K antagonist. 12. Major surgery within 14 days prior to the first dose of study drug. 13. Patient has significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 180 days prior to the first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or left ventricular ejection fraction ≤ 40%. 14. Pregnant women, those planning to become pregnant during the study, and/or breastfeeding women are ineligible for participation. 15. Patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: 1. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds). No new IV therapy or intravenous antibiotics may be initiated within 2 weeks prior to first dose of study drug. 2. Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HBsAg positive, or HBcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive) 3. Unexplained fever \> 38.3°C within 7 days prior to the first dose of study drug administration (if the fever is considered attributed to the patient's malignancy or an explained infection, the Patient may be enrolled at the discretion of the Investigator). 16. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.