KITE-753: A phase 2 study of an autologous anti-CD19/CD20 CAR T-cell therapy in CAR-naive patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).

Abstract

TPS7098 Background: CD19-directed CAR T-cell therapy has become the standard of care for R/R LBCL; however, some patients are refractory to CD19 CAR T-cell therapy and a subset of responders relapse (Eyre et al. Ann Oncol . 2025, Westin et al. N Engl J Med . 2023). KITE-753 is an investigational, bicistronic, CD19/CD20 CAR T-cell therapy with a parallel CAR design to optimally engage two tumor antigens, synergistic CD28/4-1BB costimulation to enhance T-cell function, and a rapid manufacturing process that preserves naive and stem cell memory T cells. It is designed to improve cure rates while limiting toxicity for patients with R/R LBCL. In vitro, KITE-753 demonstrated potent antitumor activity at a dose >25-fold lower than an identical product manufactured with a traditional ex vivo expansion period (Murakami et al. ASH 2024). Phase 1 assessment of KITE-753 showed very low rates of immune effector cell-associated neurotoxicity syndrome (ICANS) and no high-grade cytokine release syndrome or ICANS in patients with R/R LBCL at the intended pivotal dose level. Furthermore, high response rates were observed with 79% of patients achieving complete response (CR). CAR T-cell expansion was comparable to KITE-363 and axi-cel despite a 10-fold lower dose (Dahiya et al. ASH 2025, Dahiya et al. ASCO 2025). Based on Phase 1 outcomes, the Phase 2 dose was established as 2×10 5 CAR T cells/kg. This Phase 2 study will evaluate the safety and efficacy of KITE-753 in CAR-naive patients with R/R LBCL. Methods: In this open-label, multicenter, single-arm study, patients will undergo leukapheresis and receive optional bridging therapy, followed by lymphodepleting chemotherapy (cyclophosphamide [300 mg/m 2 /day] and fludarabine [30 mg/m 2 /day]) from Day -5 to Day -3, and infusion of KITE-753 at a target dose of 2×10 5 CAR T cells/kg on Day 0. The primary endpoint is objective response rate (CR rate + partial response rate) assessed by central review per Lugano Classification (Cheson et al. J Clin Oncol . 2014). Secondary outcomes include CR rate, duration of response, progression-free survival, overall survival, and safety. The target enrollment is 80 patients. Eligible adults have histologically confirmed R/R LBCL (including transformation of indolent lymphomas and primary mediastinal B cell lymphoma) after ≥2 prior lines of systemic therapy (including anti-CD20 mAb or bispecific antibody + anthracycline). Other key inclusion criteria are adequate bone marrow and organ function and ECOG performance status ≤2. Key exclusion criteria are prior CAR T-cell therapy or active central nervous system involvement from lymphoma. This study is currently open and actively accruing patients (NCT04989803). Clinical trial information: NCT04989803 .