Lyell launches first head-to-head CAR-T trial

Lyell Immunopharma announced that the first patient has been dosed in a first-of-its-kind  phase 3 trial, randomizing patients between different CAR T-cell therapies.

The PiNACLE – H2H phase 3 trial is evaluating Lyell’s ronde-cel, also known as LYL314, compared to Bristol Myers Squibb’s liso-cel (Breyanzi) or Gilead’s axi-cel (Yescarta) for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the second-line setting. Patients randomized 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.

 “…this trial represents a milestone in the field of cellular therapy, being the first trial to randomize patients between different CAR T-cell therapies,” said Krish Patel, MD, director, Lymphoma Research at Sarah Cannon Research Institute (SCRI).

LYL314 is designed with an ‘OR’ logic gate to target B-cells that express either CD19, CD20 or both. It is manufactured to produce a CAR-T cell product with higher proportions of naïve and central memory T-cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR-T cells with enhanced antitumor activity.

In June 2025, Lyell shared positive clinical data demonstrating high rates of durable complete responses from LYL314’s phase 1/2 trial. In patients treated in the 3L+ setting (N=25), LYL314 continued to demonstrate robust clinical responses, with an 88% overall response rate and a 72% complete response rate. Of the 3L+ patients who achieved a complete response, 71% remained in complete response at ≥ 6 months.