A Phase 2 Study of CRG-022 in Participants With Relapsed/Refractory Large B-cell Lymphoma

Inclusion Criteria: Must provide signed informed consent Must be aged ≥18 years Must have histological confirmation of LBCL Must have relapsed or refractory disease after the last therapy For enrollment in cohort 1, patients must have previously received a CD19-directed CAR T-cell therapy For enrollment in cohort 3, patients must have received at least 2 prior lines of therapy including a bispecific T-cell engaging antibody therapy Must have at least one radiographically measurable lesion Must have a washout period of at least 2 weeks or five half-lives, whichever is shorter, since any prior cancer therapy A tumor tissue sample along with a corresponding local pathology report, must be available for submission to the Sponsor Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Hematology and organ function: Absolute neutrophil count ≥ 1000/μL Platelet count ≥ 75,000/μL or ≥ 50,000/μL with known presence of marrow disease Absolute lymphocyte count ≥ 100/μL Estimated creatinine clearance ≥ 45 mL/minute Serum alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal Total bilirubin ≤ 1.5 mg/dL Cardiac left ventricular ejection fraction (LVEF) ≥45% and no evidence of pericardial effusion Blood oxygen saturation > 92% Serum albumin ≥ 2.5 g/dL Women of childbearing potential must agree to remain abstinent or use contraceptive methods Men must agree to be abstinent (refrain from heterosexual intercourse) or use a condom Able and willing to comply with the study protocol Willing and able to remain within 1 hour of the treating center for at least 4 weeks after infusion Must be stable or have recovered from nonhematologic toxicities due to prior therapy to grade ≤ 1 Exclusion Criteria: Patients who have a history of malignancy other than the lymphoma Patients with active fungal, bacterial, viral, or other infection that requires intravenous antimicrobials. Patients who received prior allogeneic stem cell or solid organ transplant Patients who received prior allogeneic CAR therapy or anti-CD52 antibody therapy Patients who received prior bispecific T-cell engaging antibody therapy (e.g., glofitamab, epcoritamab) may not be enrolled in cohort 1 Patients with history of central nervous system (CNS) involvement of lymphoma within 1 year prior to enrollment Patients with ongoing cardiac involvement of lymphoma History of CD22-directed therapy for lymphoma History of infection with any of the following: human immunodeficiency virus; hepatitis B virus or hepatitis C virus Patients with significant, uncontrolled concomitant disease including the following: History of cardiac disease within 12 months prior to enrollment Active pulmonary disease Clinically significant liver disease Clinically significant neurological disease History of autoimmune disease or requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years Patients with evidence of moderate to severe forms of primary immunodeficiencies History of severe, immediate hypersensitivity reaction attributed to aminoglycosides or any of the agents used in this study Women of child-bearing potential who are pregnant or breastfeeding Patients who underwent recent major surgery (within 4 weeks prior to leukapheresis), other than for diagnosis Patients with any in-dwelling line or drain and ommaya reservoirs History of symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation therapy within 6 months prior to enrollment Patients who received treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or who are anticipated to need such a vaccine during the course of the study Patients with Richter's transformation of CLL Patients with T cell/histiocyte-rich large B-cell lymphoma Patients who require urgent therapy due to mass effects of tumor of impending oncologic emergency Patients undergoing concurrent treatment with any other investigational agent