A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma

ABSTRACT: Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor T cell, targets and eliminates CD19/CD20-positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Patients with CD19 and/or CD20-positive R/R B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2 per day; fludarabine: 30 mg/m2 per day) followed by an IV dose of prizlon-cel. The primary end points were dose-limiting toxicity (DLT) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of the 48 patients infused prizlon-cel, 44 had large B-cell lymphoma (LBCL). No patient experienced DLT. Cytokine release syndrome occurred in 93.8% of the patients, with only 1 case of grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in 6.3% of patients, with no grade 3 or higher events. The most common grade 3 or higher TEAEs were neutropenia (83.3%) and leukopenia (50%). The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow-up of 30.0 months, median DOR, PFS, and OS were all not reached. Kaplan-Meier estimate of 2-year DOR, PFS, and OS rates were 66.0%, 62.6%, and 76.5%, respectively. Prizlon-cel had a favorable safety profile and a high and durable response in patients with R/R B-NHL, suggesting a promising treatment option for patients with R/R B-NHL. These trials were registered at www.clinicaltrials.gov as #NCT04317885, #NCT04655677, #NCT04696432, and #NCT04693676.