Biologics

Gilead CAR-T Trials on Partial Hold Over Neurotoxicity Concerns

Gilead Sciences says two clinical trials of its investigational CAR-T cell therapy KITE-753 have been placed on partial clinical hold following reports of serious neurological adverse events in a small number of patients.

The company disclosed the regulatory action during its recent third-quarter earnings call. The affected studies are PALISADES-1, a Phase 2 trial evaluating KITE-753 as second-line treatment for diffuse large B-cell lymphoma (DLBCL), and PALISADES-2, a Phase 3 trial in patients with relapsed or refractory disease receiving third-line or later treatment.

Gilead initially paused the trials voluntarily before reaching agreement with FDA on a partial clinical hold to investigate emerging safety concerns, according to a 10/30 Fierce Biotech report.

Gilead chief medical officer Dietmar Berger said the company was investigating safety differences observed between Phase 1 and Phase 2 development. Cindy Perettie, executive vice president and head of Gilead's Kite cell therapy division, said the concerns involved Grade 3 and Grade 4 immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially serious neurological complication of CAR-T treatment.

"We have made a decision to take a look at differences that we're seeing specifically with Grade 3 and Grade 4 ICANS in a small number of patients," Perettie said during the call. She emphasized that no patient deaths or Grade 5 adverse events had been reported.

KITE-753 is an investigational dual-targeting CAR-T therapy directed against CD19 and CD20. Earlier Phase 1 results had shown promising antitumor activity, including complete responses in 71% of patients in data reported for KITE-753 and a related investigational therapy.

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