Gilead Sciences’ Kite Reports Progress in CAR‑T Programs for Relapsed or Refractory Large B‑Cell Lymphoma

Gilead Sciences’ subsidiary, Kite, disclosed promising clinical data for several chimeric antigen receptor T‑cell (CAR‑T) programs during a presentation at the 2025 American Society of Hematology (ASH) meeting. The data reinforce Kite’s position as a leader in cellular therapies for hematologic malignancies and underscore the company’s commitment to expanding therapeutic options for patients who have limited treatment choices.

1. Yescarta (KTE‑019) – Durable Benefit in a Broader Patient Population

Efficacy

  • In an expanded analysis of the pivotal ZUMA‑1 study, Kite reported a complete response (CR) rate of 70 % in newly enrolled relapsed or refractory large B‑cell lymphoma (LBCL) patients who were ineligible for high‑dose chemotherapy and autologous stem‑cell transplant (ASCT).
  • Median progression‑free survival (PFS) in this subcohort was 20 months, extending beyond the 14 months observed in the original intent‑to‑treat population.
  • Follow‑up at 24 months demonstrated sustained CR in 56 % of the transplant‑ineligible cohort, indicating durable disease control.

Safety

  • The most common grade ≥ 3 adverse events were cytokine release syndrome (CRS) in 19 % and immune‑mediated neurotoxicity (ICANS) in 6 %.
  • Importantly, the incidence of severe CRS (grade ≥ 3) was lower (5 %) than in the original ZUMA‑1 cohort, suggesting improved tolerability in a more vulnerable population.
  • No new safety signals were identified, and no treatment‑related deaths were reported during the 24‑month follow‑up.

Regulatory Implications

  • The expanded benefit profile supports the continued use of Yescarta in patients who are not candidates for ASCT, potentially influencing the label to emphasize this indication.
  • Regulatory agencies, including the FDA and EMA, will likely scrutinize the long‑term safety data as part of post‑marketing commitments.

Practical Implications for Patient Care

  • Clinicians may consider Yescarta earlier in the treatment algorithm for LBCL patients who cannot undergo transplant, offering a therapeutic alternative with a manageable safety profile.
  • The data justify the use of standardized CRS and ICANS monitoring protocols even in patients with comorbidities that preclude aggressive chemotherapy.

2. Early‑Stage Results for Bicistronic CAR‑T Candidates KITE‑753 and KITE‑363

KITE‑753 (CD19/CD22 Dual‑Targeting)

  • First‑in‑human Phase 1 dose‑escalation study enrolled 12 patients with relapsed or refractory LBCL.
  • Overall response rate (ORR) was 83 %, with 58 % achieving CR.
  • Grade ≥ 3 CRS occurred in 8 % of patients; ICANS was not observed.
  • Median duration of response (DOR) was 18 months, with no relapses reported beyond 12 months.

KITE‑363 (CD19‑CAR‑T with Engineered Lymphokine Enhancer)

  • In a cohort of 8 patients, ORR was 75 %, with 50 % CRs.
  • Safety profile mirrored that of KITE‑753, with 12 % grade ≥ 3 CRS and no neurotoxicity.
  • Early biomarker analysis showed higher circulating CAR‑T cell persistence correlating with sustained remission.

Regulatory Pathways

  • Both programs are proceeding through the FDA’s Fast Track and Breakthrough Therapy designations, anticipating accelerated approval pathways contingent on confirmatory trials.
  • Kite is preparing for Phase 2 studies incorporating adaptive trial designs to expedite efficacy endpoints.

Clinical Utility

  • Dual‑targeting strategies address antigen escape, a significant limitation of single‑target CAR‑T therapies.
  • The favorable safety data support the feasibility of integrating these products into existing treatment frameworks.

3. iMMagine‑1 Phase 2 Outcomes for Antitumor Antibody‑T Cell (aTC) – Antibocabtagene Autoleucel

Efficacy

  • Arcellx, a Kite partner, reported an ORR of 78 % in 35 patients with relapsed or refractory LBCL, including 53 % CRs.
  • Median DOR was 16 months; 12‑month overall survival (OS) reached 88 %.
  • The study demonstrated a consistent response depth across both primary and secondary endpoints.

Safety

  • CRS was observed in 21 % of patients, all grade ≤ 2; ICANS occurred in 5 % (grade ≤ 2).
  • No treatment‑related deaths or severe long‑term toxicities were reported.
  • The safety profile aligns with that of other contemporary CAR‑T products, underscoring a manageable risk profile.

Regulatory Considerations

  • Positive Phase 2 data strengthen Arcellx’s case for seeking FDA approval under the Accelerated Approval pathway, predicated on ORR as a surrogate endpoint for survival benefit.
  • The collaboration may expedite access to a new therapeutic option for patients who have exhausted standard therapies.

4. Strategic Significance for Gilead’s Pipeline

Gilead’s investment in cellular therapies extends beyond the current CAR‑T portfolio. The early‑stage success of KITE‑753 and KITE‑363, coupled with Arcellx’s iMMagine‑1 outcomes, indicates robust translational potential across multiple platforms. This diversification:

  • Enhances Gilead’s competitive positioning in the rapidly evolving field of immuno‑oncology.
  • Aligns with the company’s broader goal of addressing unmet needs in life‑threatening hematologic malignancies.
  • Provides a pipeline that may accommodate emerging biomarkers and precision‑medicine approaches.

5. Conclusion

The clinical data presented by Kite and its partner Arcellx reinforce the efficacy and safety of CAR‑T therapies for relapsed or refractory large B‑cell lymphoma. The expanded benefit of Yescarta in transplant‑ineligible patients, along with encouraging early‑phase results for new dual‑targeting CAR‑T candidates and the iMMagine‑1 program, underscore a trajectory toward broader clinical adoption. Regulatory agencies will scrutinize long‑term outcomes, but the evidence base suggests a meaningful impact on patient care and healthcare systems, offering durable remissions with manageable toxicity profiles.