Lyell Redesigns Colorectal Cancer Trial for Potential Pivotal Expansion
Lyell reported Grade 2 or worse diarrhea or colitis fell from 55% to 10% with gastrointestinal prophylaxis and a new safety protocol.
Lyell Immunopharma, Inc. (LYEL), a late-stage developer of cancer cell therapies, amended its colorectal cancer study to accommodate potential pivotal testing, extending a program whose previous updates had centered on patient dosing and dose escalation. The change followed new safety results for LYL273, although the company had not yet determined the maximum tolerated dose and said pivotal expansion requires discussions with regulators.
The progression marked the main development across Lyell’s recent updates. In March, the company reported seven newly treated patients since acquiring the program in November 2025. Its May update highlighted the start of dosing at Dose Level 3. The latest amendment established a Phase 1/2 structure that enables seamless expansion into a potential pivotal single-arm Phase 2 trial once the recommended dose is determined, subject to FDA discussions.
The safety update covered 19 patients with relapsed or refractory metastatic colorectal cancer at a May 5 cutoff. Ten received gastrointestinal prophylaxis and a new safety management protocol, while nine received no prophylaxis. Grade 2 or worse diarrhea or colitis occurred in 10% of the prophylaxis group, compared with 55% of those without prophylaxis.
The preventive regimen included infliximab, vedolizumab and budesonide before symptoms developed. No patients receiving prophylaxis experienced Grade 3 or worse diarrhea or colitis, cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. CAR T-cell expansion kinetics were similar between the groups. The amended study also added cohorts for second-line treatment and a combination with radiotherapy.
Lyell’s more advanced lymphoma program continued along its existing development timetable. Ronde-cel, which targeted CD19 and CD20, remained under evaluation in two pivotal trials: PiNACLE for patients receiving third-line or later treatment, and PiNACLE-H2H in the second-line setting. Lyell expects additional PiNACLE data in the second half of 2026 and pivotal data in mid-2027.
The company presented updated ronde-cel safety findings covering more than 100 patients at the European Hematology Association congress in June. The Phase 1/2 results included no Grade 3 or worse cytokine release syndrome and low rates of severe neurological toxicity. Manufacturing success was 97%. The safety findings supported the potential for outpatient administration.
PiNACLE-H2H continued enrolling after patient dosing began in February. The randomized trial compared ronde-cel with investigators’ choice of axicabtagene ciloleucel or lisocabtagene maraleucel, with event-free survival as its primary endpoint. Lyell expects a progress update in the second half of 2026, alongside the additional data anticipated from its other clinical studies.
Clinical activity also shaped the quarter’s expenses. Research and development spending was $39.5 million, compared with $34.9 million a year earlier. The increase was primarily attributable to greater clinical trial activity: research activities, collaborations and outside services increased $8.8 million, partly offset by a $4.2 million reduction in facilities and personnel expenses.
The second-quarter net loss widened to $44.8 million from $42.7 million in the same period of 2025. The increase was principally attributable to higher research spending and lower interest income, partly offset by lower equipment disposal losses and an impairment charge that did not recur. General and administrative expenses were $9.6 million.
Cash, cash equivalents and marketable securities totaled $228.0 million at June 30, compared with approximately $261 million at March 31. The earlier balance followed the closing of a second $50 million private-placement tranche. Lyell maintained its expectation that available resources will cover working capital and capital expenditure needs into the third quarter of 2027.
The next regulatory discussion concerned LYL273: Lyell expects additional third-line or later colorectal cancer data and an End-of-Phase 1 FDA meeting in the second half of 2026. For ronde-cel, the company expects a biologics license application submission in the second half of 2027, following the anticipated pivotal readout.
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