Large B-cell lymphoma (LCBL) refers to several subtypes of non-Hodgkin lymphoma (NHL), with diffuse large B-cell lymphoma (DLCBL) being the most common and aggressive form of the disease. Large B-cell lymphomas are cancers that start in the lymphocytes and act as immune cells called B lymphocytes, which are a type of white blood cell.  KITE-363 is a promising investigational CAR T-cell therapy currently under development. This autologous treatment is designed to simultaneously target both CD19 and CD20 antigens, offering dual-targeting potential. Preclinical studies have shown that KITE-363 exhibits strong antigen-specific activity against each target. However, the therapy remains unapproved globally, and its safety and efficacy have not yet been confirmed in clinical settings.

As per the results presented at EHA 2025, the response data highlights the strong efficacy of the therapy, particularly at Dose Level 3, where CAR-naive patients (n = 23) achieved an impressive overall response rate (ORR) of 87%, including a complete response (CR) rate of 78%, indicating deep and durable remissions. In contrast, patients treated at Dose Levels 1 and 2 (n = 11) showed a lower ORR of 64%, with a CR rate of 36%, suggesting that higher dosing enhances therapeutic outcomes. Notably, among patients with LBCL who had received two or more prior lines of therapy (n = 7), both ORR and CR rates reached 100%, while primary refractory LBCL patients (n =1 5) achieved ORR and CR rates of 80% and 67%, respectively, reinforcing the drug’s activity in difficult-to-treat subgroups. Additionally, even among those with prior CAR-T exposure (n = 3), one patient achieved a CR, indicating potential utility in post-–CAR–T settings. Overall, the data support a favorable efficacy profile, particularly with higher dosing, in relapsed/refractory lymphoma populations.

In the Phase Ia study of KITE-363, no dose-limiting toxicities were observed, and the overall safety profile was manageable, with adverse events primarily hematologic in nature. At Dose Level 3, all patients experienced AEs, and 81% had Grade ≥3 events, including neutropenia (31%), anemia (15%), and decreased WBC/neutrophil counts (42%). Serious AEs occurred in 54% of patients, though severe cardiac events were rare. CRS was reported in 92% of patients at Dose Level 3 (mostly Grade 1/2), and ICANS in 46%, with only three Grade 3 ICANS events across all doses. Median CRS onset was earlier (3.5 days) and lasted longer (5 days) at this level. AE management largely involved tocilizumab and corticosteroids. Importantly, no Grade ≥3 CRS or ICANS events occurred in primary refractory LBCL patients at Dose Level 3, indicating a favorable tolerability profile in this high-risk group.

KOL insights

“These results support KITE-363 as a promising therapeutic approach for patients with relapsed/refractory B-cell lymphoma, including those with highly refractory LBCL. KITE-363 cell expansion was dose-dependent, with markedly robust expansion observed in DL3, appearing greater than 3 to 5 fold higher than with axicabtagene ciloleucel.” – Expert Opinion

Conclusion

LBCL is a group of fast-growing non-Hodgkin lymphomas, with diffuse large B-cell lymphoma (DLBCL) being the most common and marked by abnormal proliferation of infection-fighting B-cells.  KITE-363 showed a favorable safety profile and strong clinical activity in relapsed/refractory LBCL, with high response rates and robust CAR T-cell expansion, supporting its potential in both oncology and autoimmune indications.  YESCARTA’s established efficacy and commercial success provide a strong foundation within the CAR T-cell space, with global sales rising from USD 264 million in 2018 to USD 1.5 billion in 2024, and potential peak revenues projected to exceed ~USD 2 billion before patent expiry next decade. As the market evolves toward next-generation, dual-targeted therapies, emerging candidates like KITE-363 will be assessed against this benchmark, shaping the future treatment landscape.

KITE-363 represents a promising next-generation CAR T-cell therapy with several potential advantages over approved CD19-directed treatments such as YESCARTA (axicabtagene ciloleucel), KYMRIAH (tisagenlecleucel), and BREYANZI (lisocabtagene maraleucel). These approved therapies have shown substantial clinical benefit in B-cell lymphomas; however, their long-term effectiveness can be limited by antigen escape, where malignant cells downregulate or lose CD19 expression, leading to relapse. KITE-363 addresses this challenge through a bicistronic design that targets both CD19 and CD20, two antigens commonly co-expressed on B-cell lymphomas. This dual-targeting approach may enhance tumor recognition, broaden therapeutic coverage, and improve the durability of response. By potentially overcoming resistance mechanisms seen with single-antigen therapies, KITE-363 could reduce relapse risk and deliver more sustained outcomes.