ACE1831-001

Adults >=18y with histologically confirmed CD20+ aggressive B-NHL, >=2 prior systemic regimens including anthracycline and anti-CD20 chemoimmunotherapy, measurable disease, ECOG 0-1 (or ECOG 2 with albumin >3.5), adequate organ function.

Inclusion Criteria (Detailed): To be eligible, all inclusion criteria must apply: 1) Signed informed consent. 2) Male or female >=18 years at informed consent. 3) Minimum weight 50 kg (110 lbs) required at Dose Level 3 (1000 x 10^6 cells). 4) Histologically confirmed B-cell NHL (WHO 2016), including: - DLBCL, NOS - High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements - High-grade B-cell lymphoma, NOS - Transformation of FL or MZL to DLBCL - Primary mediastinal B-cell lymphoma - Follicular lymphoma grade 3B - Burkitt lymphoma - Monomorphic post-transplant lymphoproliferative disorder, DLBCL type 5) Persistent/progressive B-cell lymphoma after at least 2 prior systemic therapies per NCCN; prior therapies must include at minimum an anthracycline-containing and an anti-CD20 monoclonal-containing chemoimmunotherapy regimen. 6) >=1 measurable lesion by revised IWG response criteria for malignant lymphoma (Cheson 2014). - Previously irradiated lesions are measurable only if progression documented post-radiation. - If PET-negative and only nodal disease on CT, at least one lymph node must be >=2 cm. 7) ECOG 0-1, or ECOG 2 with serum albumin >3.5. 8) Adequate hematologic function, independent of platelet transfusion and growth factor support for >=14 days before planned lymphodepletion: - Platelets >100,000/mm3 (100 x 10^9/L) - ANC >=1500/mm3 (1.5 x 10^9/L) 9) Adequate renal/hepatic/cardiac function: - Creatinine clearance >60 mL/min (Cockcroft-Gault) OR eGFR >60 mL/min/1.73 m2 (4-variable MDRD) - AST/ALT <=3.0 x ULN (or <5.0 x ULN if liver lymphomatous involvement) - Total bilirubin <=2.5 x ULN (except Gilbert syndrome) - Albumin >=3.0 g/dL - LVEF >=50% and no clinically significant pericardial effusion by ECHO/MUGA 10) Oxygen saturation by pulse oximetry >=92% at rest on room air. 11) Women of childbearing potential and all males must agree to >=1 highly effective contraception method (<1% failure rate) during screening, throughout study treatment, and for 1 year after lymphodepleting chemotherapy. - Males not sexually abstinent with partners of childbearing potential must use condom during sexual contact with pregnant females or females of childbearing potential as required by protocol.

CNS lymphoma/meningeal disease, active significant infection, uncontrolled major comorbidities, recent anticancer/cellular/monoclonal therapy within protocol washouts, unresolved significant prior-treatment toxicities, active HBV/HCV/HIV not meeting protocol exceptions, pregnancy/lactation.

Participants are excluded if any of the following are present: 1) Detectable CSF malignant cells, brain metastases, CNS lymphoma, or primary CNS lymphoma. - History of CNS lymphoma may be eligible only if treated, neurologically stable, no corticosteroid requirement, and no recent MRI evidence of lesion growth. - Suspected meningeal involvement requires lumbar puncture/cytology to exclude malignant cells. 2) Clinically relevant CNS disorder history/presence (e.g., epilepsy/seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, PRES, autoimmune disease with CNS involvement). 3) History of other malignancy except protocol-allowed cases: - Curatively treated and no known active disease >=2 years, low recurrence risk - Adequately treated non-melanoma skin cancer/lentigo maligna without disease - Adequately treated carcinoma in situ without disease 4) Clinically significant active infection requiring IV antibiotics currently or within 7 days before planned lymphodepletion (exceptions include simple UTI/bacterial pharyngitis or prophylactic anti-infectives). 5) HIV infection by screening labs, except participants on ART >=4 weeks with HIV viral load <400 copies/mL may be eligible. 6) Active HBV or HCV by screening labs; HBV/HCV protocol-defined virologic suppression/management exceptions may apply. 7) Any serious/unstable medical, psychiatric, familial, or social condition that in investigator/medical monitor judgment impairs safe treatment or protocol compliance. 8) Unresolved toxicities from prior anticancer therapy not recovered to CTCAE v5.0 Grade <=1 (except alopecia, vitiligo, and lab values meeting eligibility). 9) Concurrent systemic immunosuppressants (e.g., cyclosporine/tacrolimus) within 14 days of planned lymphodepletion, or chronic prednisone >10 mg/day within 14 days (limited steroid exceptions allowed). 10) Systemic anticancer therapy washout violations: - Chemotherapy/targeted small molecule within 2 weeks or 5 half-lives (whichever longer) - Monoclonal antibody therapy within 4 weeks - Approved/investigational cellular therapy within 8 weeks 11) Live vaccine <=6 weeks prior to initial screening. 12) Pregnant or lactating female, or unwillingness to practice required birth control from consent through 1 year after lymphodepletion.