Lyell Immunopharma Doses First Patient in Phase 3 Head-to-Head CAR T-Cell Trial for Lymphoma
Lyell Immunopharma has initiated dosing in its Phase III PiNACLE – H2H trial, comparing ronde-cel against approved CAR T-cell therapies for relapsed or refractory large B-cell lymphoma in second-line treatment.
Lyell Immunopharma has dosed the first patient in its PiNACLE – H2H Phase III chimeric antigen receptor (CAR)-cell trial for relapsed or refractory (r/r) large B-cell lymphoma (LBCL). The head-to-head study compares rondecabtagene autoleucel (ronde-cel, LYL314) with lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients receiving second-line treatment.
The trial randomly assigns patients with r/r LBCL who will receive either ronde-cel at a dose of 100 x 10⁶ CAR T cells or the investigator's choice of liso-cel or axi-cel as per their product labels. The primary endpoint is event-free survival. The trial aims to enroll nearly 200 patients per arm (N = 400), including those with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, Grade 3B follicular lymphoma, or transformed mantle cell lymphoma who have not previously received CAR T-cell therapy, among others.
Ronde-cel is also being evaluated in the pivotal single-arm PiNACLE trial in third- or later-line treatment settings. This study will enroll 120 patients at nearly 25 sites and uses a dose of 100 x 10⁶ CAR T cells. The primary endpoint is the overall response rate.
In the third- or later-line cohort, a best overall response rate of 93% and a complete response rate of 76% were observed among 29 efficacy-evaluable patients. Median progression-free survival was 18 months as of 5 September 2025. In the second-line cohort, 18 efficacy-evaluable patients demonstrated an 83% overall response rate and a 61% complete response rate.
The chief medical officer stated that data from the single-arm pivotal PiNACLE trial in patients with later-stage large B-cell lymphoma are expected to be submitted for marketing approval to the FDA next year. The company described PiNACLE – H2H as the first-of-its-kind Phase III head-to-head randomized controlled CAR T-cell trial, demonstrating confidence in ronde-cel's potential to be the best-in-class CAR T-cell treatment for patients with relapsed or refractory disease.
In June 2025, Lyell reported new clinical data from the Phase I/II clinical trial of autologous dual-targeting CD19/CD20 CAR T-cell product candidate, LYL314, along with data from those with LBCL in the third or later line (3L+) setting. Lyell acquired ronde-cel when it bought startup ImmPact Bio in 2024, and has since positioned the therapy as its lead research candidate.