KITE-363 Shows High Response in B-Cell Lymphoma With Manageable Safety

Among patients with relapsed/refractory B-cell lymphoma, the anti-CD19/CD20 CAR T-cell therapy KITE-363 showcased high response rates with a manageable safety profile, according to results from a first-in-human phase 1 study presented during the 2025 ASCO Annual Meeting.

Safety data indicated that no dose-limiting toxicities were reported in phase 1a. Grade 3 (severe) or higher side effects were experienced by 2 patients who received the agent at dose level 1 (DL1; 3 patients), which was 0.5 x 10⁶ CAR T cells/kg. Grade 3 or higher side effects were reported in six patients who received dose level 2 (DL2; 8 patients), which was 1 x 10⁶ CAR T cells/kg. In those who received dose level 3 (DL3; 26 patients), which was 2 x 10⁶ CAR T cells/kg, the most common grade 3 or higher side effects included decreased white blood cell count (11 patients), neutropenia (8 patients) and decreased neutrophil count (11 patients).

Moreover, one grade 3 case of cytokine release syndrome (CRS) was reported in a patient with nodular lymphocyte-predominant Hodgkin lymphoma; the duration of the event was one day. Three grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS) events were observed: one in the DL2 group, which had a duration of four days, and two in the DL3 group, which had durations of one and two days, respectively. Notably, no grade 3 or higher CRS or ICANS events were observed in those with primary refractory large B-cell lymphoma who received the CAR T-cell therapy at DL3 (15 patients).

In patients without prior exposure to CAR T-cell therapy who received KITE-363 at DL3 (23 patients), the objective response rate was 87%, and this was comprised of a complete response rate of 78% and a partial response rate of 9%. Four percent of patients had stable disease and 9% had progressive disease. Within this group, those with large B-cell lymphoma who had previously received at least two lines of therapy (seven patients) experienced an objective response rate and complete response rate of 100% each. Those with primary refractory large B-cell lymphoma (15 patients) experienced an objective response rate of 80% and a complete response rate of 67%. Of the 3 patients who had prior CAR T exposure and received DL3, one achieved a complete response.

Among those who received KITE-363 at DL1 and DL2 (11 patients), the objective response rate was 64%, with a complete response rate of 36% and a partial response rate of 27%. Nine percent experienced stable disease and 27% had progressive disease.

“These results support KITE-363 as a promising therapeutic approach for patients with relapsed/refractory B-cell lymphoma including those with highly refractory large B-cell lymphoma,” Saurabh Dahiya, MD, FACP, an associate professor of medicine at Stanford University School of Medicine in Stanford, California, said in a presentation of the data.

Keeping Up With KITE-363 and Its Evaluation in R/R B-Cell Lymphoma
The bicistronic, lentiviral-encoded autologous CAR T-cell therapy, KITE-363, is dual targeted. The anti-CD19 and anti-CD20 CAR possess a CD28 costimulatory domain and a 4-1BB costimulatory domain, respectively. “Dual targeting has the potential to address tumor heterogeneity and improve the durability of responses by preventing CD19-negative relapses,” Dahiya noted.

The open-label, multicenter, phase 1 study utilized a 3 plus 3 study design. It was comprised of a phase 1a dose-escalation portion and a phase 1b dose-expansion portion. For phase 1a, patients had histologically confirmed relapsed/refractory B-cell lymphoma by World Health Organization criteria following more than two lines of therapy or second-line primary refractory disease. Phase 1b only enrolled patients with relapsed/refractory large B-cell lymphoma, which included those with second-line primary refractory disease. All patients were at least 18 years of age and had an ECOG performance status of 0 or 1.

They were excluded if they had Richter transformation, central nervous system involvement of lymphoma, active infection, or a central nervous system disorder of clinical significance. Those with clinically significant autoimmune or cardiac disease were also excluded.

The primary end points for phase 1a and phase 1b were incidence of dose-limiting toxicities and objective response rate, respectively. Secondary end points included complete response rate, duration of response, progression-free survival, time to next treatment, overall survival, safety, and levels of CAR T cells and cytokines in the blood.

After screening, patients were enrolled and underwent leukapheresis. This was followed by optional bridging therapy, which was comprised of corticosteroids with or without local radiation therapy per investigator discretion. From day –five to –three, patients received lymphodepleting chemotherapy comprised of cyclophosphamide at 300 milligrams per square meter (mg/m²) daily and fludarabine at 30 mg/m² daily for three days. On day 0, patients were infused with KITE-363 at one of the three dose levels. For DL3, the median time from leukapheresis to infusion with the CAR T-cell therapy was 27 days. The first post-infusion response assessment was conducted on day 28.

A total of 41 patients were enrolled and underwent leukapheresis. Three of these patients were not treated, and the remaining 38 went on to receive lymphodepleting chemotherapy. Because one patient did not meet protocol-required eligibility to receive KITE-363, a total of 37 patients received the CAR T-cell therapy.

At the data cutoff date of March 18, 2025, the median follow-up in those who received treatment (37 patients) was 12.4 months. The median follow-up for those in the DL3 group was 11.1 months.

The median age for all treated patients was 62 years, with 46% aged 65 years or older and 11% aged 75 years or older. In the DL3 group, the median age was 60.5 years, with 42% aged 65 years or older and 12% aged 75 years or older. More than half of patients were male (65%), most were White (78%), most were not Hispanic or Latino (86%) and had an ECOG performance status of 1 (60%). Moreover, 73% of all treated patients had stage III or 4 disease at study entry, as did 65% of those in the DL3 group.

In all treated patients, the most common histologic subtype was large B-cell lymphoma (92%), followed by indolent non-Hodgkin lymphoma (5%) and nodular lymphocyte-predominant Hodgkin lymphoma (3%). In the DL3 group, the most common histologic subtype was also large B-cell lymphoma (96%), followed by nodular lymphocyte-predominant Hodgkin lymphoma (4%). Nineteen percent of all treated patients and 15% of those in the DL3 group had bulky disease, which was defined as at least 7.5 centimeters. Dahiya noted that patients had tumors that were positive for CD19 and/or CD20, with most patients (78%) having tumors that were positive for both. Thirteen percent of patients had tumors that were positive for 1 antigen.

In all treated patients, 46% were primary refractory and 54% had received two or more prior regimens. Nineteen percent received prior CD19-targeted CAR T-cell therapy, 14% previously underwent autologous stem cell transplant and 57% had received bridging therapy. In the DL3 group, 58% were primary refractory and 42% had received at least two prior lines of treatment. In the 15 patients who were primary refractory, four experienced partial responses as best response to frontline treatment and 11 experienced progressive disease. Prior CD19-targeted CAR T-cell therapy and prior autologous stem cell transplant were received by 12% and 15% of patients, respectively. Fifty-eight percent of patients in this group received bridging therapy.

Additional Efficacy Data

The median duration of complete response, defined as duration of response of all patients who achieved a complete response as best response, was not reached. The duration of complete response rate at 6 months was 71.4%. “Data beyond 6 months is heavily impacted by censoring,” Dahiya noted. “Longer follow-up is needed.” Nine of the 37 patients who received treatment died; 8 died due to progressive disease.

Safety Spotlight

Among those who received the CAR T-cell therapy at DL3, all patients experienced any-grade side effects. Eighty-one percent of these effects were grade 3 or higher. Any-grade and grade 3 or higher serious side effects were reported in 54% and 38% of patients, respectively. Any-grade cardiac disorders were experienced by 35% of patients; 4% were grade 3 or higher. Any-grade infections occurred in 42% of patients; 15% were grade 3 or higher. Hematologic side effects included neutropenia (any grade, 38%; grade 3 or higher, 31%), thrombocytopenia (8%; 4%) and anemia (31%; 15%). Hypogammaglobulinemia occurred in 15% of patients.

In those who received KITE-363 at DL1 or DL2, grade 1 or 2 CRS occurred in 64% of patients and grade 3 ICANS occurred in 9%. The median time to onset of CRS was six days and the median duration was three days. The median time to onset of ICANS was also 6sixdays and the median duration was six days. CRS was managed with Actemra in 45% of patients and corticosteroids in 27%. ICANS was managed with corticosteroids in 9% and Kineret in 9%.

In those who received the agent at DL3, grade 1 (mild) or 2 (moderate) CRS occurred in 88% and grade 3 CRS occurred in 4%. The median time to onset was 3.5 days and the median duration was five days. Most events were managed with Actemra (88%), followed by corticosteroids (65%) and Kineret (4%). Grade 1 or 2 ICANS was experienced by 38%; this effect was grade 3 for 8%. The median time to onset was six days and the median duration was 4.5 days. These effects were largely managed with corticosteroids (38%) followed by Kineret (15%).

Additional Revelations and Take-Home Message

“KITE-363 cell expansion was dose dependent, with markedly robust expansion observed in DL3, appearing greater than 3- to 5-fold higher than with Yescarta,” Dahiya said. Post-infusion peak levels of serum analytes were also linked with KITE-363 pharmacokinetics and reduced toxicity.

Due to these early results, the robust CAR T-cell expansion and the acceptable toxicity profile, the agent is also under development for patients with autoimmune disease, Dahiya concluded.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.