KITE-753 Trials in R/R DLBCL Placed on Partial Clinical Hold for ICANS

The PALISADES-1 (NCT04989803) and PALISADES-2 (NCT07479797) trials evaluating the investigational anti-CD19/CD20 CAR T-cell therapy KITE-753 in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have been placed on a partial clinical hold, according to Gilead Sciences’ third-quarter 2026 earnings call held on October 29, 2026.¹ The hold allows Gilead and its cell therapy subsidiary Kite to investigate differences in high-grade immune effector cell–associated neurotoxicity syndrome (ICANS) observed between the phase 1 and phase 2 portions of the KITE-753 development program.

Why were the PALISADES trials placed on a partial clinical hold?

According to Dietmar Berger, MD, PhD, chief medical officer of Gilead Sciences, during an earnings call, the developers paused the 2 trials to investigate safety differences noted between the phase 1 and phase 2 safety findings.²

In response to an analyst question about rapid manufacturing, Cindy Perettie, executive vice president and head of Gilead’s cell therapy division Kite Pharma distinguished KITE-753, which is produced with a 3-day manufacturing process, from KITE-363, a structurally identical construct made with conventional manufacturing. Kite’s phase 1 studies of KITE-363 in rheumatologic and neurologic autoimmune diseases do not use rapid manufacturing and are continuing. The developer stated that it will provide updates as more information becomes available.

What are the PALISADES-1 and PALISADES-2 trials?

PALISADES-1 is an open-label, multicenter phase 1/2 study of KITE-363 or KITE-753 in adults with relapsed/refractory B-cell lymphoma. Primary end points include the incidence of dose-limiting toxicities (DLTs) in phase 1a and investigator-assessed objective response rate (ORR) per Lugano 2014 criteria in phase 1b.³ At the 2025 American Society of Hematology (ASH) Annual Meeting, investigators said the data supported further development of KITE-753.⁴

PALISADES-2 is a randomized, open-label, multicenter phase 3 trial comparing KITE-753 with axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory large B-cell lymphoma (LBCL) after 1 prior line of therapy.⁵ Its primary end point is to evaluate the efficacy of KITE-753 vs axi-cel, specifically 6-month complete response (CR) and event-free survival.

What did early data show for KITE-753?

KITE-753 and KITE-363 are bicistronic autologous CAR T-cell therapies built on Kite’s DuoCore construct, which pairs anti-CD19 and anti-CD20 targeting with dual CD28 and 4-1BB costimulation. KITE-753 uses a novel manufacturing process intended to preserve T-cell fitness.

In phase 1 data presented at ASH 2025, 30 patients received KITE-753. At a median follow-up of 2.9 months at dose level 3 (0.2 × 10⁶ CAR T cells/kg), 11 of 14 CAR-naive patients (79%) achieved a complete response (CR); across all dose levels, 14 of 20 CAR-naive patients had a CR. No DLTs were observed, and no grade 3 or higher cytokine release syndrome (CRS) or ICANS occurred at dose level 3.

How does the KITE-363 safety profile compare?

Data for KITE-363 presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting included 37 treated patients, 26 of whom received dose level 3 (2 × 10⁶ CAR T cells/kg).⁶ Among 23 CAR-naive patients at dose level 3, the ORR was 87% and the CR rate was 78%. Grade 3 ICANS occurred in 2 patients (8%) at dose level 3 and lasted 1 and 2 days, respectively; there were no grade 4 or 5 CRS or ICANS events, and no DLTs occurred in phase 1a.

References

1. Gilead Sciences, Inc. Q3 2026 earnings call summary. News release. Moby Intelligence. October 30, 2026. Accessed November 2, 2026. https://tinyurl.com/4327r5ep
2. Gibney M. Gilead reveals partial clinical hold on 2 CAR-T cell therapy trials. Fierce Biotech. October 30, 2026. Accessed November 2, 2026. https://tinyurl.com/59s36ypt
3. Study of KITE-363 or KITE-753 in participants with relapsed and/or refractory B-cell lymphoma (PALISADES-1). ClinicalTrials.gov. Updated October 28, 2026. Accessed November 2, 2026. https://tinyurl.com/2d5d4vkk
4. Kite’s next-generation bicistronic CAR T-cell therapies show encouraging phase 1 results in relapsed/refractory B-cell lymphoma in new data at ASH 2025. News release. Gilead Sciences, Inc. December 6, 2025. Accessed November 2, 2026. https://tinyurl.com/y2jheut7
5. Study evaluating the efficacy of KITE-753 versus axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma after first-line therapy (PALISADES-2). ClinicalTrials.gov. Updated October 26, 2026. Accessed November 2, 2026. https://tinyurl.com/37r2bee9
6. Dahiya S, 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. J Clin Oncol. 2025;43(suppl 16):7003. Presented at: 2025 ASCO Annual Meeting; May 30–June 3, 2025; Chicago, IL.