Lyell Immunopharma amends LYL273 trial to Phase 1/2 design following safety gains

Lyell Immunopharma (NASDAQ:LYEL) announced on Monday that it has amended its ongoing U.S. Phase 1 clinical trial for LYL273 to a Phase 1/2 design.

The transition follows successful safety updates that demonstrate a marked improvement in the management of adverse events for patients with relapsed or refractory metastatic colorectal cancer (mCRC).

The company reported that the implementation of a new gastrointestinal (GI) prophylaxis regimen has substantially improved the therapy's safety profile.

Among patients receiving the prophylaxis, the incidence of Grade 2 or higher diarrhea or colitis fell to 10%, down from 55% in earlier cohorts.

Furthermore, no occurrences of Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in the prophylaxis-treated group.

Nineteen patients have been treated across the first two dose levels, and dose escalation is continuing, with the maximum tolerated dose yet to be determined.

The trial amendment enables a seamless expansion into a potential pivotal single-arm Phase 2 study, pending regulatory alignment with the U.S. Food and Drug Administration (FDA).

The expanded design adds new cohorts—including those for second-line treatment and patients receiving radiotherapy in combination with LYL273—targeting a total enrollment of approximately 84 patients across the Phase 1 and Phase 2 segments.

LYL273 is a guanylyl cyclase C (GCC)-targeted CAR T-cell therapy enhanced with CD19 CAR expression and controlled cytokine release.

It is designed to navigate and overcome the challenging tumor microenvironment typical of solid tumors. The candidate has already received Fast Track designation from the FDA.

Lyell plans to present additional Phase 1 clinical data and conduct an End-of-Phase 1 meeting with the FDA in the second half of 2026.