Lyell Immunopharma upgrades LYL273 to Phase 1/2 design
Lyell Immunopharma has amended its ongoing US Phase 1 trial of LYL273 to a Phase 1/2 design, setting up a seamless pathway into a potential pivotal single-arm Phase 2 study once the recommended Phase 2 dose is established — subject to alignment with the US Food and Drug Administration. The South San Francisco-based company simultaneously released updated safety data showing that a gastrointestinal prophylaxis regimen markedly reduced the colitis signal that had been a central concern for the programme.
As of a 5 May 2026 data cutoff, nineteen patients had been enrolled across Dose Levels 1 and 2 in the trial. Ten of those patients received a GI prophylaxis protocol combining infliximab, vedolizumab and budesonide alongside a standardised safety management plan. Under that regimen, the incidence of Grade 2 or higher diarrhoea or colitis fell from 55% in the nine patients treated without prophylaxis to 10% in the ten patients who received it — a clinically meaningful reduction in a toxicity that had complicated earlier dosing. No Grade 3 or higher cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was observed in patients managed under the new protocol, and there were no additional adverse events of interest.
Safety management without compromising cell expansion
A key question for any prophylaxis strategy in CAR T-cell therapy is whether immunosuppressive agents might blunt the very cellular response the therapy depends upon. Lyell reported no difference in GCC-CAR-positive cell expansion — either in peak expansion or area under the curve — between patients who received GI prophylaxis and those who did not. That finding, if it holds at higher dose levels, materially reduces the trade-off concern and strengthens the case for taking the prophylaxis approach into later-stage cohorts.
Dose escalation is continuing; the maximum tolerated dose has not yet been determined, and the trial now includes four dose-escalation cohorts at 1, 2, 3 and 4 × 10⁶ CAR-positive cells per kilogram, each designed to enrol three to six patients.
Trial expansion and near-term milestones
The amended CARABINER trial adds new cohorts beyond the existing third-line-or-later mCRC population, including a second-line cohort and a cohort evaluating LYL273 in combination with radiotherapy. Up to sixty patients are expected across the new cohorts. New trial centres are being activated in preparation for the dose-expansion phase.
Lynn Seely, president and chief executive, said the absence of Grade 3 or higher CRS and ICANS in patients managed under the new safety plan suggested the programme's tolerability profile was becoming addressable. An End-of-Phase 1 meeting with the FDA and additional clinical outcome data, including efficacy readouts, are expected in the second half of 2026.
LYL273 holds FDA Fast Track designation for mCRC. A 50% overall response rate across Dose Levels 1 and 2 was previously reported from a data cutoff of October 2025, though Lyell has not yet disclosed detailed response-durability metrics.
Market context
Solid-tumour CAR T-cell therapy remains one of the hardest problems in oncology cell therapy. Approved CAR T products have demonstrated transformative results in haematological malignancies, but the immunosuppressive and physically dense solid-tumour microenvironment has frustrated most programmes targeting carcinomas. Lyell's approach — combining GCC targeting with CD19 CAR co-expression and cytokine-release engineering — is designed to improve immune-cell infiltration and persistence in that hostile environment.
Colorectal cancer carries a large unmet need in the relapsed/refractory setting, where options are limited and overall survival is poor. Several other cell-therapy and tumour-infiltrating lymphocyte programmes are advancing in gastrointestinal cancers, meaning Lyell will need convincing Phase 2 efficacy data to differentiate LYL273 in an increasingly crowded field.