Lyell doses first patient in Phase III trial for LBCL

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 PiNACLE – H2H study compares rondecabtagene autoleucel (ronde-cel, LYL314) with lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients receiving second-line treatment.

It 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 enrol 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 enrol 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.

Lyell Immunopharma chief medical officer David Shook said: “Data from Lyell’s 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.

“We are now pleased to have underway PiNACLE – H2H, the first-of-its-kind Phase III head-to-head randomised controlled CAR T-cell trial. This strategy demonstrates Lyell’s 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.

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