KITE-363 Shows Potential As a Next-Generation CAR T-Cell Therapy for R/R LBCL

September 26, 2025

Saurabh Dahiya, MD, FACP, discussed how the unique mechanism of action of KITE-363 may improve upon the efficacy of other CAR T-cell therapies for LBCL.

Phase 1 trial (NCT04989803) findings suggest that the dual-targeting CAR T-cell therapy KITE-363 may overcome a major limitation of current CAR T-cell therapies—antigen escape—and maintain the strong response rates and manageable toxicity profile seen with other CAR T-cell products in patients with relapsed/refractory large B-cell lymphoma (LBCL), according to Saurabh Dahiya, MD, FACP.1

“There's still an unmet need and a need to develop the next generation of CAR T-cell therapy,” Dahiya said in an interview with OncLive®.

In the interview, Dahiya discussed the rationale for trying to overcome antigen escape in patients with relapsed/refractory LBCL, how the unique mechanism of action of KITE-363 may improve upon the efficacy of previously developed CAR T-cell therapies, and preliminary safety and efficacy data observed with the agent in this population.

KITE-363 Phase 1 Trial in LBCL: Key Takeaways

The safety profile of KITE-363 was considered manageable, and no DLTs were observed in Phase 1a. At dose level 3 (n = 26), most CRS events were grade 1/2 (88%).
KITE-363 generated high response rates in the highly refractory CAR T-cell therapy–naive LBCL population at dose level 3 (n = 23). In this group, the ORR was 87%, with a CR rate of 78%.
KITE-363 cell expansion was dose dependent, with markedly robust expansion observed at dose level 3. The median peak level of CAR T cells/µl in CAR T-cell therapy–naive patients at dose level 3 was 132.3.

Dahiya is an associate professor of medicine at Stanford University School of Medicine, as well as clinical director of Cancer Cell Therapy in the Division of Blood and Marrow Transplantation and Cell Therapy at Stanford Health Care in California.

OncLive: What was the rationale for investigating KITE-363 in patients with relapsed/refractory B-cell lymphoma?

Dahiya: Autologous CAR T-cell therapies have revolutionized the treatment of patients with relapsed/refractory LBCL. However, most patients still experience [disease] relapse after receiving CAR T-cell therapy.

How prevalent is CD19 antigen escape in patients with relapsed/refractory LBCL?

Since the FDA approvals of autologous CD19-directed therapy, several publications have shown that approximately one-third of patients [with LBCL who receive these therapies] experience either antigen downregulation or antigen-negative, CD19-negative relapses. At Stanford, our own research has shown that approximately one-third of the patients experience either CD19 downregulation or complete CD19 escape.2 This [finding] was published in a few large studies, both in our single-institution study, as well as in multi-institutional, real-world consortium–based studies.

What is the mechanism of action of KITE-363? What makes this agent unique compared with other CAR T-cell therapies?

KITE-363 is a dual-targeting bicistronic CAR T-cell therapy directed against CD19 and CD20. The intent with this therapy is to overcome antigen escape by dual targeting. The CAR T itself has 2 costimulatory domains: 4-1BB for the CD20-directed CAR and CD28 for the CD19-directed CAR. This confers the CAR T cell a distinct behavioral characteristic in terms of expansion kinetics, as well as effector function. We think that by dual targeting, we can decrease the antigen escape phenomena and increase the immunologic pressure on the lymphoma. By having these 2 different costimulatory molecules, we may be able to improve upon the toxicity and efficacy in the treatment of patients with relapsed/refractory LBCL.

What was the design of the phase 1 study evaluating KITE-363 in patients with relapsed/refractory B-cell lymphoma?

The study was conducted in phase 1a and 1b portions.1 The phase 1a portion followed a 3 x 3 dose-escalation design, where we started with the lowest dose level [of KITE-363] at 0.5 x 106 CAR-positive cells per kg of recipient body weight; that was dose level 1. Dose level 2 was 1 x 106 CAR-positive cells/kg, and dose level 3 was 2 x 106 CAR-positive cells/kg. The dose-expansion portion of the study was done at the highest dose level, at 2 million CAR-positive cells/kg.

What were the key safety findings in the phase 1 trial of KITE-363?

The primary end point of this study was [the incidence of] dose-limiting toxicities [DLTs]. We did not observe any DLTs [in the phase 1a portion], and as such, we were able to reach the highest dose level. In terms of safety, at the highest dose level, in CAR T-cell therapy–naive patients, we did not see any grade 3, 4, or 5 cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome events in the intended population of patients with LBCL that was relapsed/refractory.

What was the efficacy of KITE-363 in LBCL?

At the highest dose level, in CAR T-cell therapy–naive patients, we observed an overall response rate of 87% and a complete response [CR] rate of 78%. The durability of these responses appeared [to be] good. The median duration of CR [DOCR] was not yet reached. The estimated 6-month [DOCR rate] was 71.4% in this high-risk patient population.

References

Dahiya A, Ulrickson M, Topp M, et al. A phase 1 study of KITE-363 anti-CD19/CD20 chimeric antigen receptor T-cell therapy in patients with relapsed/refractory B-cell lymphoma. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S236.
Spiegel J, Oak JS, Goyal A, et al. CD19 antigen density down-regulation at time of progression in large B-cell lymphoma patients treated with axicabtagene ciloleucel. Transplant Cell Ther. 2024;30(suppl 2):S204. doi:10.1016/j.jtct.2023.12.265