A phase 1 study of KITE-363 anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy in patients (pts) with relapsed/refractory (R/R) B-cell lymphoma (BCL).

7003 Background: Approximately 30% of pts with R/R LBCL who relapse after CAR T-cell therapy experience CD19 antigen escape (Spiegel et al. Blood. 2021).KITE-363 is a bicistronic, autologous CAR T-cell therapy that can potentially prevent CD19 escape through upfront dual targeting of CD19 and CD20. Here we report safety and preliminary efficacy from an open-label, multicenter Phase 1 study of KITE-363 in R/R BCL. Methods: Eligible adults had LBCL, indolent NHL, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), or mediastinal gray zone lymphoma R/R after ≥2 lines of therapy (LoT). Pts with LBCL may have had primary refractory disease after ≥1 LoT. Study included dose escalation (1A) and expansion (1B; LBCL only) cohorts. After lymphodepleting chemotherapy, pts received KITE-363 at dose levels (DLs) 1, 2, or 3 (0.5×10 6 , 1×10 6 , or 2×10 6 CAR T cells/kg, respectively). Primary endpoints were incidence of dose-limiting toxicities (DLTs; Phase 1A) and investigator-assessed objective response rate (ORR per Lugano; Phase 1B). Results: As of 10/14/2024, 41 pts enrolled and 37 received KITE-363 (see table). For pts with LBCL (n = 34), 50% were primary refractory and 44% had IPI 3-4. No DLTs occurred. Grade ≥3 adverse events (AEs) occurred in 76% of treated pts and serious AEs in 49%. Grade 3 cytokine release syndrome (CRS; per Lee et al. 2014) occurred in 1 pt (3%; NLPHL; DL 3); Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 pts (8%; 1 DL 2; 2 DL 3); no Grade ≥4 CRS/ICANS occurred. Median onset of ICANS was 6 d with median duration of 5 d, and median onset of CRS was 4 d with median duration of 5 d. Six pts died (5 to progression; 1 to myelodysplastic syndrome concurrent with LBCL relapse, unrelated to KITE-363). At 7.3 months median follow-up, ORR in CAR-naive pts at DL 3 was 87%; complete response (CR) rate was 78%. Among those, all 7 pts with LBCL who were CAR-naive after ≥2 LoT had a CR. Those in DL 3 who were primary refractory (n = 15) had an 80% ORR (CR rate, 67%). Median duration of response was not reached. In all pts at DL 3 (n = 26), median CAR T-cell expansion peak, area under the curve (AUC), and time to peak were 121.5 cells/µL, 711.1 cells/µL×d, and 10 d, respectively. For CAR-naive pts in DL 3, median peak and AUC were 132.2 cells/µL and 819.2 cells/µL×d; medians in those with prior CAR T-cell therapy (n = 3) were 5.7 cells/µL and 85.7 cells/µL×d, respectively. Conclusions: No DLTs occurred in Phase 1A. Safety profile of KITE-363 was tolerable, with no Grade ≥3 CRS in pts with LBCL and 2 cases of Grade 3 ICANS at the highest DL. KITE-363 demonstrated high responses in pts with highly refractory BCL, including those with primary refractory disease. Clinical trial information: NCT04989803 . Baseline characteristics. Treated Pts (N=37) a Median age, y (range) 62 (25-83) ECOG 1 59 Stage III/IV 73 ≥3 prior LoT 41 Prior CAR T-cell exposure 19 a Percent unless otherwise specified.