SANTA MONICA, Calif. –– Kite, a Gilead Company (Nasdaq: GILD), presented Phase 1 data today with encouraging efficacy and safety results for its two investigational bicistronic CAR T-cell therapies, KITE-753 and KITE-363, respectively, in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). The results of the analysis were shared in an oral presentation (Abstract #265) at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.
Both KITE-753 and KITE-363 are bicistronic autologous CAR T-cell therapies. They are designed to target two antigens (CD19 and CD20) found on cancer cells and use two co-stimulatory domains (CD28 and 4-1BB) to help the immune system fight cancer more effectively. The KITE DuoCore™ construct – with two independent CARs working synergistically – may prevent relapse by reducing cancer cells escaping treatment and may help improve safety, making it possible to treat more patients outside of a hospital setting. Additionally, KITE-753 leverages a novel manufacturing process that preserves T-cell fitness. Combined, these attributes may contribute to better efficacy, lower toxicity, durable function, and faster delivery to patients.
“While CAR T-cell therapy has revolutionized treatment for many people with blood cancers, we urgently need options that not only improve upon the curative potential of existing cell therapies for evasive cancers but are also safer and available to a broader patient population,” said Dr. Saurabh Dahiya, MD, FACP, the Stanford School of Medicine. “The encouraging response rates, durability and safety profile of KITE-753 and KITE-363 offer strong clinical evidence to support further development.”
The open-label, multicenter, umbrella Phase 1 study enrolled 67 patients with R/R BCL. Thirty patients received KITE-753 and 37 received KITE-363.
Results for KITE-753 showed that at a median follow-up of 4.0 months overall and 2.9 months at dose level three (DL3; 0.2×106 CAR T cells/kg), 11 of 14 CAR-naïve patients (79%) receiving DL3 had a complete response, where the cancer completely disappeared. Bridging options in this Phase 1 study were limited to corticosteroid +/- radiation therapy, and all patients had measurable, active disease at the time of their infusion with KITE-753. No patients responded to these bridging therapy measures at DL3. Notably, KITE-753 demonstrated robust expansion despite a tenfold lower dose than DL3 of KITE-363 (2×106 CAR T cells/kg), which highlights the proliferative capacity of KITE-753. Across all dose levels, 14 of 20 CAR-naïve patients achieved a complete response.
Overall, KITE-753 showed an encouraging safety profile with no dose‑limiting toxicities. At DL3, no Grade ≥3 cytokine release syndrome (CRS) or immune effector cell‑associated neurotoxicity syndrome (ICANS) were observed; Grade ≥3 adverse events occurred in 95% of patients (primarily cytopenias), and serious Grade ≥3 adverse events occurred in 26% of patients. Across all dose levels, one Grade 3 CRS event (none Grade ≥4) and no Grade ≥3 ICANS events occurred.
“Kite is dedicated to pushing the boundaries of CAR T-cell therapy to deliver even greater impact and curative potential,” said Dr. Gallia Levy, Senior Vice President, Global Head of Development at Kite. “By combining CD19/CD20 targeting with dual co‑stimulation, along with a manufacturing process resulting in a fit product, we aim to improve outcomes. Our goal is to bring CAR T to more patients, such as those with advanced disease who have exhausted other options, and to those who prefer to be treated in outpatient and in community oncology practice settings.”
Meanwhile, results for KITE-363 revealed that at a median follow-up of 17.5 months, there was a durable benefit at the highest dose level (2×106 CAR T cells/kg) among CAR-naïve patients, with more than 70% of complete responders evaluable at 12 months remaining in remission. KITE-363 was generally well tolerated with no dose-limiting toxicities or severe side effects that required stopping the study. Grade ≥3 CRS occurred in one patient; Grade 3 ICANS occurred in two patients; no Grade ≥4 CRS/ICANS occurred.
About LBCL
Globally, large B-cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma. In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30–40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.
About the Study
Thirty patients received KITE-753 and 37 received KITE-363. The open-label, multicenter umbrella Phase 1 study enrolled eligible adults with R/R LBCL after ≥2 lines of therapy (patients with LBCL could have second-line primary refractory disease) in dose escalation (1A) and expansion (1B; LBCL only) cohorts. Following leukapheresis and lymphodepletion, patients received dose level (DL) 1, 2, or 3 of KITE-753 (3.0×104, 1.0×105, or 2.0×105 CAR T cells/kg, respectively) or KITE-363 (0.5×106, 1×106, or 2×106 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).
About KITE-753 and KITE-363
KITE-753 and KITE-363 are investigational, bicistronic autologous CAR T-cell therapies engineered to overcome tumor antigen heterogeneity and prevent relapse. The KITE DuoCore™ construct uniquely combines anti-CD19 and anti-CD20 targeting with dual co-stimulation (CD28 and 4-1BB). KITE-753 is an enhanced KITE DuoCore™ CAR T utilizing a novel manufacturing process, aiming to preserve T-cell fitness. Additionally, KITE-363 is being investigated for refractory autoimmune conditions.
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For more information on Kite, please visit the company’s website at www.kitepharma.com. Follow Kite on social media on X and LinkedIn.
Ashleigh Koss, Media
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Jacquie Ross, Investors
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