Lyell Immunopharma initiates PiNACLE - H2H, a Phase 3 CAR T-cell therapy trial.

Lyell Immunopharma has initiated PiNACLE - H2H, a Phase 3 clinical trial comparing ronde-cel, a next-generation CD19/CD20 CAR T-cell therapy, to approved CD19 CAR T-cell therapies in second-line aggressive large B-cell lymphoma patients. A Steering Committee of lymphoma experts has been established to advise on the trial design and conduct. Ronde-cel aims to deliver improved complete response rates and longer duration of responses compared to current CD19 CAR T-cell therapies.

Lyell Immunopharma, Inc. (Nasdaq: LYEL) has announced the initiation of PiNACLE - H2H, a Phase 3 clinical trial comparing rondecabtagene autoleucel (ronde-cel) to approved CD19 CAR T-cell therapies in patients with second-line aggressive large B-cell lymphoma (LBCL). The trial, which will evaluate event-free survival, is designed to enroll approximately 400 patients and is expected to begin enrolling patients by early 2026 [1].

Ronde-cel, a dual-targeting CD19/CD20 CAR T-cell therapy, aims to deliver improved complete response rates and longer duration of responses compared to current single-antigen-targeting CD19 CAR T-cell therapies. The therapy is designed with an 'OR' logic gate to target B cells that express either CD19, CD20, or both, each with full potency. Additionally, 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 [1].

A Steering Committee of preeminent lymphoma experts has been established to advise on the design and conduct of this groundbreaking head-to-head clinical trial. The committee includes distinguished members from leading institutions such as the University of Chicago, Moffitt Cancer Center, University of Colorado, University of Nebraska Medical Center, Sarah Cannon Research Institute, and The University of Texas MD Anderson Cancer Center [1].

The trial will compare ronde-cel to lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) for patients with relapsed or refractory (R/R) large B-cell lymphoma receiving treatment in the second line (2L) setting. Patients randomized to ronde-cel will be treated with a dose of 100 x 106 CAR T cells, and the primary endpoint of the trial is event-free survival. Patients may be treated with ronde-cel in either the inpatient or outpatient setting and are required to remain near the treating center for 14 days [1].

Lyell is also advancing a single-arm pivotal trial of ronde-cel in the third- or later-line (3L+) setting, which is expected to enroll approximately 120 patients. This trial aims to evaluate the overall response rate and is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial of ronde-cel [1].

Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the U.S. Food and Drug Administration (FDA) for the treatment of patients with R/R LBCL in the 3L+ setting. These designations are intended to expedite the development and review of the therapy [1].

The trial is expected to provide valuable data on the potential clinical benefits of ronde-cel compared to current CD19 CAR T-cell therapies, which could have significant implications for the treatment of aggressive large B-cell lymphoma. As the trial progresses, investors and financial professionals will closely monitor the results to assess the potential impact on Lyell's pipeline and market position [1].

References:
[1] https://www.globenewswire.com/news-release/2025/09/03/3143517/0/en/Lyell-Immunopharma-Announces-the-Initiation-of-a-Phase-3-Head-to-Head-CAR-T-Cell-Therapy-Clinical-Trial-in-Aggressive-Large-B-Cell-Lymphoma-and-Formation-of-Expert-Steering-Committ.html