CD19/20-Targeted KITE-363 Elicits Strong Response in LBCL

Saurabh Dahiya, MD

Stanford University School of Medicine

KITE-363 elicited responses in nearly all patients with relapsed/refractory large B-cell lymphoma (LBCL) who were treated with the dual CD19 and CD20-directed chimeric antigen receptor (CAR) T-cell therapy, according to data from a phase 1 study (NCT04989803) presented at the 2025 ASCO Annual Meeting.

For the single-arm dose escalation study, KITE-363 was administered at 3 dose levels (DL), with the largest dose selected for further study. In CAR T cell-naive patients treated with this dose (n = 23), the objective response rate (ORR) was 87%, which included a complete response (CR) rate of 78%. At 6 months, 71.4% of patients who experienced a CR continued to respond to treatment. The median duration of response had not yet been reached and there were not any dose-limiting toxicities observed.

"The response appeared durable with an immediate duration of complete response that has not been reached," said lead investigator Saurabh Dahiya, MD, from Stanford University School of Medicine. "At the RP2D among patient with primary refractory LBCL—which is the key intended patient population for this drug's future development—we observed no grade 3 or 4 cytokine release syndrome or ICANS in this study, which is a sharp contrast to the current FDA-approved CAR T-cell therapies."

In the dose escalation study, the median age of enrolled patients was 62 years across the full study and 60.5 years in the RP2D arm. Of those enrolled, 11% were 75 years of age or older. Stage III/IV disease was present for most patients (73%). Half of patients had received 2 or more prior lines of therapy (54%), including a prior CAR T-cell therapy for 3 patients in the RP2D arm and by 7 in the full study. Most patients had LBCL histology (92%), with the study also enrolling 2 patients with indolent non-Hodgkin lymphoma and 1 patient with nodular lymphocyte-predominant Hodgkin lymphoma.

The first DL was 0.5 x 10⁶, the second was 1 x 10⁶, and the third and RP2D was 2 x 10⁶ CAR T cells per kg. The process began with aphaeresis followed by off-site manufacturing, which took a mean of 27 days to complete (range, 21-56). Lymphodepleting chemotherapy was administered with cyclophosphamide at 300 mg/m²/day and fludarabine at 30 mg/m²/day, which was given 5 and 3 days prior to the infusion of the manufactured CAR T cells. The lymphodepleting regimen was notably less intense than the standard of care with other FDA approved CAR T-cell therapies, Dahiya said.

For patients with LBCL who received 2 or more lines of therapy, the CR rate with the RP2D was 100%. In those with primary refractory LBCL, the ORR was 80% and the CR rate was 67%. For the lower doses combined (n = 11), the ORR was 64% in patients treated with KTE-363, these responses included a CR rate of 36%.

In the DL3 group of CAR T cell naive patients (n = 23), the median CAR T cell expansion peak was 132.3 cells per µL, with a median time to peak of 9 days. The area under the curve (AUC) was 819.2 cells/µL x days. For comparison, Dahiya showed data from the ZUMA-1 cohort 4 and ZUMA-7 trials looking at axicabtagene ciloleucel (Yescarta). The peak CAR T cell expansion in ZUMA-1 was 52.9 cells/µL and in ZUMA-7 it was 25.8 cells/µL.

"Looking at the expansion kinetics, KTE-363 demonstrated pronounced expansion across all dose levels with higher expansion seen with the higher dose levels," said Dahiya. "The robust expansion in this particular study is likely is function of synergistic activity of the dual CARs that are expressed on T cells."

A grade 3 or greater adverse event (AE) was experienced by 81% of patients treated with KTE-363. Serious AEs were seen in 38%. Across all doses, there was only 1 case of grade 3 cytokine release syndrome (CRS) and 3 patients experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). In the RP2D dose, grade1/2 CRS was seen in 88% and grade 1/2 ICANS was seen in 38% of patients. In the RP2D dose, the median time to onset of ICANS was 6 days and the median duration was 4.5 days. The median time to onset of CRS was 3.5 days and the median duration was 5 days.

In the RP2D arm, 88% of patients received tocilizumab and 65% received a corticosteroid to manage CRS. For ICANS, 38% of patients received corticosteroids to manage the AE. Anakinra was given for 1 patient with CRS and for 4 with ICANS.

"The management is very similar to what is done to other cell therapies," said Dahiya. When describing why he felt the AEs were lower with KTE-363 vs other CAR T cells, he said, "In my opinion, the CD19 portion of the CAR is similar but the CD20 portion of the CAR changes the dynamics. These could be effective synergistic activators. Those analyses of course still need to be done."

REFERENCE

Dahiya S, Ulrickson M, Topp M, et al. 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). J Clin Oncol. 2025;43 (suppl 17; abstr 7003). Doi: 10.1200/JCO.2025.43.16_suppl.7003.