Lyell Immunopharma Targets Mid-2027 Pivotal Data for Lymphoma CAR-T Therapy

Key Points

• Lyell expects pivotal PiNACLE trial data in mid-2027 for ronde-cel in large B-cell lymphoma after at least two prior treatments, with a biologics license application targeted for year-end 2027 after the full data set is available.
• In later-line patients, ronde-cel showed a 91% overall response rate and a 77% complete response rate; 75% of complete responders remained in remission at 12 months. The company reported no severe cytokine release syndrome events, though longer follow-up is needed.
• Lyell is enrolling a 400-patient Phase 3 trial comparing ronde-cel with Yescarta or Breyanzi in second-line patients, using event-free survival as the primary endpoint. Its manufacturing center can produce over 3,000 doses annually, with a reported 98% success rate in delivering product to patients.

Lyell Immunopharma NASDAQ: LYEL expects pivotal data in mid-2027 for its lead CAR-T cell therapy, ronde-cel, as the company advances the treatment in patients with large B-cell lymphoma who have received at least two prior lines of therapy.

President and CEO Dr. Lynn Seely said Lyell is completing enrollment in the single-arm PiNACLE trial and expects the last patient to be treated by year-end. The company plans to submit a biologics license application after the full data set is available. During the discussion, the operator described the planned submission as targeted for year-end 2027.

Ronde-cel targets two proteins, CD19 and CD20, and is manufactured using a process intended to increase the proportion of naive T cells in the product. Seely said the design aims to improve complete response rates and response durability while maintaining a manageable safety profile.

Response and safety data

In the third-line or later setting, ronde-cel achieved a 91% overall response rate and a 77% complete response rate, according to figures discussed on the call. Of those who achieved a complete response, 75% remained in complete response at 12 months. Median progression-free survival had not been reached, while the estimated 24-month progression-free survival rate was 54%.

Dr. Alexander Boardman, an associate physician at Mass General Brigham Cancer Institute, called the results encouraging compared with outcomes typically seen with existing CAR-T treatments. He cautioned, however, that comparisons across studies are limited by differences in eligibility criteria and patient characteristics.

Boardman said the third-line data showed no severe cytokine release syndrome events and a relatively low incidence of immune effector cell-associated neurotoxicity, or ICANS. He also noted that Lyell uses preventive dexamethasone, a steroid, and said the field has mixed data on how steroid exposure affects CAR-T efficacy. In his view, moderate-dose preventive treatment is generally acceptable, although higher doses may carry risks.

Seely said the PiNACLE trial’s primary endpoint is overall response rate and that regulators will also consider response duration. She expressed confidence in the potential for approval based on the data reported so far, while acknowledging that commercialization depends on regulatory clearance.

Head-to-head trial in earlier treatment

Lyell is also enrolling a randomized Phase 3 trial, PiNACLE-H2H, in second-line patients. The study will compare ronde-cel with an investigator’s choice of Yescarta or Breyanzi, two approved CD19-directed CAR-T therapies.

The trial is designed to enroll 400 patients, with 200 in each arm, and its primary endpoint is event-free survival. Results for Yescarta and Breyanzi will be pooled for the comparison, Seely said. The study includes an interim analysis as well as a final analysis, but she did not specify the hazard ratio the trial is powered to detect.

Seely said most trial centers are open and recruitment has exceeded the company’s expectations. She added that the study will include about 60 centers, largely in the United States.

For a separate second-line cohort, an abstract showed a 95% overall response rate and a 76% complete response rate. Among patients who achieved a complete response, 92% remained in complete response at six months. Boardman described the results as compelling, particularly because a substantial proportion of patients had primary refractory disease, which he said is difficult to treat.

Manufacturing and commercial plans

Seely said Lyell’s manufacturing center can produce more than 3,000 CAR-T doses annually at full capacity. She reported a 98% success rate in delivering product to patients and a median vein-to-ship time of 16 days.

Lyell’s initial commercial goal, if ronde-cel is approved, is to compete with existing CD19 CAR-T therapies. Seely also sees an opportunity to expand treatment use among eligible patients who do not currently receive CAR-T therapy. Boardman said ronde-cel could be attractive if approved, citing its safety profile, dual targeting and reported manufacturing performance, while emphasizing the need to assess results as follow-up matures.

About Lyell Immunopharma (NASDAQ:LYEL)

Lyell Immunopharma, Inc is a clinical-stage biotechnology company focused on developing cellular therapies for the treatment of cancer. The company aims to improve the durability and effectiveness of T-cell therapies by addressing challenges such as T-cell exhaustion, limited persistence, and inadequate activity within solid tumors.

Lyell's research and development programs use technologies designed to reprogram and rejuvenate T cells, including approaches involving genetic engineering, epigenetic modification, and chimeric antigen receptor (CAR) T-cell therapy.

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