Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation

Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Assent, when appropriate, will be obtained per institutional guidelines * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Histologically confirmed diagnosis of Richter transformation (RT; transformed CLL). Only patients who have diffuse large B-cell lymphoma histology in transformation are eligible (for example, patients with transformation into Hodgkin lymphoma subtype are not eligible) * Evidence of CD20 positivity at screening (by immunohistochemistry \[IHC\] or flow cytometry) * Treatment naïve or relapsed/ refractory disease. Patients with either previously untreated RT and previously treated RT are eligible, regardless of whether or not they had received CLL-directed therapy * Radiographically measurable lymphadenopathy (≥ 1.5 cm) or splenomegaly, or bone marrow involvement by diffuse large B cell lymphoma (DLBCL)/RT * Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy * Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement * With bone marrow involvement: ANC ≥ 500/mm\^3 * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement * Without bone marrow involvement: Platelets ≥ 50,000/mm\^3 * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements * With bone marrow involvement: Platelets ≥ 25,000/mm\^3 * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements * With bone marrow involvement: Hemoglobin (Hgb) ≥ 7 g/dL * Total bilirubin ≤ 2 x upper limit of normal (ULN) or ≤ 3 x ULN for Gilbert's disease or compensated hemolysis directly attributable to CLL * Aspartate aminotransferase (AST) ≤ 3 x ULN * Alanine aminotransferase (ALT) ≤ 3 x ULN * Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ≤ 5 x ULN if attributed to lymphoma involvement of the liver * Serum creatinine ≤ 1.5 x ULN OR creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula * If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN * If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants * If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN * If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants * Left ventricular ejection fraction (LVEF) ≥ 45% * Note: To be performed within 28 days prior to day 1 of protocol therapy * Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) and no history of HIV OR * If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * Women of childbearing potential (WOCBP): Negative serum pregnancy test * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of study therapy. Sperm donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include: * Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated ≥ 2 menstrual cycles prior to screening * Intrauterine device (IUD); intrauterine hormone-releasing system (IUS) * Bilateral tubal ligation/occlusion * Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study patient and that the partner has obtained medical assessment of surgical success for the procedure) * Sexual abstinence, only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the clinical trial facilitation group guidance. Pregnancy testing and contraception are not required Exclusion Criteria: * Allogeneic bone marrow or organ transplant within 6 months or evidence of active graft versus host diseae (GVHD) * Prior CD20-targeted bispecific antibody therapy * Chronic systemic corticosteroid use \> 10 mg/day of prednisone or equivalent within 72 hours (h) of start of study treatment. Patients who received corticosteroid treatment with ≤ 10 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 10 days