Lyell Doses First Patient in Phase III Trial for LBCL

Why It Matters

The trial could establish ronde‑cel as a superior second‑line CAR‑T therapy, reshaping treatment standards for aggressive B‑cell lymphomas and unlocking significant market share. Success would also validate head‑to‑head CAR‑T comparisons, accelerating regulatory pathways for novel cell therapies.

Key Takeaways

• First patient dosed in Phase III head‑to‑head CAR‑T trial.
• Ronde‑cel dose: 100 × 10⁶ CAR T cells.
• Trial compares ronde‑cel vs liso‑cel or axi‑cel.
• Primary endpoint: event‑free survival in 400 patients.
• Earlier data show 93% overall response in later‑line cohort.

Pulse Analysis

The market for chimeric antigen receptor therapies has expanded rapidly, yet large B‑cell lymphoma remains a high‑mortality arena where durable remissions are scarce. Traditional chemo‑immunotherapy often fails in relapsed or refractory settings, prompting clinicians to turn to CAR‑T products that target CD19. Lyell’s dual‑targeting CD19/CD20 construct aims to overcome antigen escape, a common resistance mechanism, and its entry into a Phase III trial signals confidence in both efficacy and manufacturing scalability.

Head‑to‑head Phase III designs are rare in the cell‑therapy space, where most approvals stem from single‑arm studies. By directly comparing ronde‑cel with established agents lisocabtagene maraleucel and axicabtagene ciloleucel, the PiNACLE‑H2H trial will generate comparative effectiveness data that regulators and payers value. If ronde‑cel demonstrates superior event‑free survival, it could shift clinical algorithms toward earlier use, potentially displacing current second‑line standards and influencing pricing negotiations across the CAR‑T market.

For investors, Lyell’s progression from promising single‑arm outcomes—93 % overall response in third‑line patients—to a pivotal randomized trial de‑risches risk and opens a pathway to a multi‑billion‑dollar indication. A successful FDA filing next year would not only broaden Lyell’s product portfolio but also set a precedent for future head‑to‑head CAR‑T trials, accelerating innovation cycles. Stakeholders should monitor enrollment milestones, interim safety signals, and the eventual event‑free survival readout as key catalysts for the company’s valuation.

Lyell doses first patient in Phase III trial for LBCL

Lyell Immunopharma doses first patient in PiNACLE · H2H Phase III CAR‑T trial · February 13 2026

The Phase III head‑to‑head PiNACLE – H2H trial randomly assigns patients with relapsed or refractory LBCL. Credit: Motortion Films / Shutterstock.com.

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 × 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 × 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 its 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.