Lyell Immunopharma Doses First Patient in Phase 3 CAR T-Cell Trial, Reports Improved Safety Data
Lyell Immunopharma initiated the Phase 3 PiNACLE–H2H trial of ronde-cel in large B-cell lymphoma and reported that GI prophylaxis reduced severe diarrhea rates from 55% to 10% in the Phase 1 LYL273 trial.
Lyell Immunopharma has dosed the first patient in the Phase 3 PiNACLE–H2H clinical trial, which evaluates the safety and efficacy of the dual-targeting CAR T-cell therapy rondecabtagene autoleucel (ronde-cel) against existing approved CD19 CAR T-cell therapies in patients with aggressive large B-cell lymphoma receiving second-line treatment. The company also reported that gastrointestinal prophylaxis reduced the incidence of Grade ≥ 2 diarrhea or colitis from 55% to 10% in the Phase 1 trial of LYL273 for patients with relapsed or refractory metastatic colorectal cancer (mCRC).
The PiNACLE–H2H trial, the first head-to-head randomized controlled trial comparing CAR T-cell therapies, aims to randomize approximately 400 patients, with 200 patients per treatment arm. The primary endpoint is event-free survival. Ronde-cel has previously shown a high overall response rate in patients with relapsed or refractory large B-cell lymphoma. The company is also progressing with a pivotal trial for ronde-cel in later-line treatment settings and expects to file for regulatory approval in 2027. Ronde-cel has received RMAT and Fast Track designations from the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
In the amended U.S. Phase 1 trial of LYL273, the introduction of gastrointestinal prophylaxis reduced Grade ≥ 2 diarrhea/colitis from 55% to 10%, while the maximum tolerated dose has not yet been determined. Earlier reported data showed a 50% overall response rate, and no difference was observed in GCC CAR T-cell expansion kinetics in patients with or without GI prophylaxis. The trial has been amended to allow a potential seamless transition into a pivotal Phase 2 trial pending regulatory approval. Ongoing efforts will assess new cohorts, including those receiving radiotherapy in combination with the therapy. LYL273 has been granted Fast Track designation by the FDA for metastatic colorectal cancer. Further clinical data is anticipated in late 2026, alongside an End-of-Phase 1 FDA meeting.