Lyell Immunopharma has begun its PiNACLE – H2H Phase III trial evaluating rondecabtagene autoleucel (ronde-cel, also known as LYL314) compared to lisocabtagene maraleucel (liso-cel) or axicabtageneciloleucel (axi-cel). 

The CAR-T therapies will be assessed in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the second-line (2L) setting. 

“Ronde-cel is a dual-targeting CD19/CD20 CAR T-cell product candidate that has demonstrated impressive clinical data in patients with aggressive large B-cell lymphoma,” said Krish Patel, Director of Lymphoma Research at Sarah Cannon Research Institute (SCRI). “One of our SCRI CAR T-cell sites is the first to enroll in this important trial designed to provide physicians the data we need to make the best treatment decisions for our patients.  

“Furthermore, this trial represents a milestone in the field of cellular therapy, being the first trial to randomise patients between different CAR T-cell therapies.” 

In the trial, patients randomised to ronde-cel will be treated with a dose of 100 x 106 CAR T cells; patients in the control arm will be treated as per the product label. The primary endpoint of this superiority trial is event-free survival and the trial plans to enroll approximately 200 patients per arm with R/R LBCL. 

The trial will include patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular or transformed mantle cell lymphoma who have not previously received CAR-T therapy.  

“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,” said David Shook, Lyell’s Chief Medical Officer. “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.” 

Ronde-cel clinical trial results 

At the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025, Lyell reported positive updated clinical data in patients with aggressive LBCL in the 3L+ and 2L settings from the Phase I/II trial. The oral presentation included updated data from the 3L+ cohort (now the ongoing PiNACLE pivotal trial), including a best overall response rate of 93% and a complete response rate of 76% in 29 efficacy-evaluable patients with R/R LBCL. The median progression-free survival was 18 months as of the data cutoff date of 5 September 2025.  

Updated data were also presented from the 2L cohort, including 18 efficacy evaluable patients (94% with high-risk primary refractory disease), and demonstrated an 83% best overall response rate and a 61% complete response rate. Data from 25 patients treated with ronde-cel and receiving dexamethasone prophylaxis revealed no reports of Grade 3 or higher cytokine release syndrome (CRS) and one case (4%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS). 

Ronde-cel is also being studied in PiNACLE, a pivotal single-arm trial in the third- or later-line (3L+) setting. This registration trial is a seamless expansion of the 3L+ cohort from the Phase I/II trial and will enrollapproximately 120 patients at approximately 25 sites. The dose is 100 x 106 CAR T cells and the primary endpoint is overall response rate.