Lyell Immunopharma Announces Initiation of Patient Dosing in First-of-Its-Kind Phase 3 Head-To-Head CAR T-Cell Clinical Trial in Aggressive Large B-Cell Lymphoma

Rhea-AI Summary

Lyell Immunopharma (Nasdaq: LYEL) dosed the first patient in PiNACLE – H2H, a Phase 3 randomized head-to-head trial of rondecabtagene autoleucel (ronde-cel) versus liso-cel or axi-cel in second-line relapsed/refractory large B-cell lymphoma. The trial plans ~400 patients (200 per arm) and uses event-free survival as the primary endpoint.

Ronde-cel showed a 93% best overall response rate and 76% complete response rate in 29 efficacy-evaluable 3L+ patients; median progression-free survival was 18 months (data cutoff Sept 5, 2025). A BLA submission for the pivotal 3L+ trial is expected in 2027.

Positive

• Phase 3 randomized head-to-head trial enrolling ~400 patients (N=400)
• Reported 93% best overall response rate in 3L+ cohort
• Reported 76% complete response rate in 3L+ cohort
• Median progression-free survival of 18 months (data cutoff Sept 5, 2025)
• BLA submission for 3L+ pivotal trial expected in 2027

Negative

• Efficacy data from small cohorts: 29 and 18 efficacy-evaluable patients
• One reported Grade 3+ ICANS (4%) despite outpatient-suitable safety profile

Key Figures

PiNACLE–H2H size: N = 400 (200 per arm) PiNACLE size: 120 patients Ronde‑cel dose: 100 x 10^6 CAR T cells +5 more

8 metrics

PiNACLE–H2H size N = 400 (200 per arm) Phase 3 head‑to‑head 2L LBCL trial

PiNACLE size 120 patients Pivotal single‑arm 3L+ LBCL trial

Ronde‑cel dose 100 x 10^6 CAR T cells Dose used in both PiNACLE–H2H and PiNACLE

3L+ ORR 93% Best overall response rate in 29 efficacy‑evaluable 3L+ LBCL patients

3L+ CR rate 76% Complete response rate in 29 efficacy‑evaluable 3L+ LBCL patients

3L+ median PFS 18 months Median progression‑free survival as of Sept 5, 2025 cutoff

2L ORR 83% Best overall response rate in 18 efficacy‑evaluable 2L LBCL patients

Grade ≥3 ICANS 4% 1 of 25 patients with dexamethasone prophylaxis

Market Reality Check

Price: $24.34 Vol: Volume 97,198 is 1.09x th...

normal vol

$24.34 Last Close

Volume Volume 97,198 is 1.09x the 20-day average of 89,371, showing slightly elevated interest pre-announcement. normal

Technical Shares at $24.34 are trading above the 200-day MA of $16.27, reflecting a pre-existing uptrend before this trial update.

Peers on Argus

LYEL was up 2.66% while peers were mixed: CADL (-4.33%), IVVD (-3.59%), ALLO (-2...

LYEL was up 2.66% while peers were mixed: CADL (-4.33%), IVVD (-3.59%), ALLO (-2.06%), AVIR (+6.70%), NMRA (+2.39%). This pattern points to stock-specific drivers rather than a broad biotech move.

Previous Clinical trial Reports

5 past events · Latest: Dec 07 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 07	ASH data update	Positive	+12.3%	High ORR/CR and durable PFS data for ronde‑cel in LBCL at ASH.
Nov 03	ASH presentations	Positive	-0.7%	Announcement of two ASH oral presentations with encouraging ronde‑cel data.
Sep 03	Phase 3 initiation	Positive	+0.2%	Launch of PiNACLE–H2H head‑to‑head Phase 3 CAR T trial in LBCL.
Jun 17	Positive Phase 1/2 data	Positive	-4.6%	Strong LYL314 response rates and durability with manageable safety in LBCL.
May 01	Upcoming ICML data	Positive	-1.1%	Announcement of upcoming ICML oral presentation of new LYL314 data.

Pattern Detected

Clinical trial news has generally been positive, but price reactions have been mixed, with 3 negative and 2 positive moves following prior clinical updates.

Recent Company History

Over the past year, LYEL has repeatedly highlighted strong ronde‑cel clinical data in aggressive LBCL, progressing from Phase 1/2 results into pivotal PiNACLE and Phase 3 PiNACLE–H2H programs. Prior clinical updates showed high response rates, durable remissions, and favorable safety suitable for outpatient use. Market reactions to these clinical trial announcements have been inconsistent, sometimes rising on strong data (e.g., Dec 7, 2025) and sometimes drifting lower despite positive news. Today’s initiation of Phase 3 dosing continues this established development trajectory.

Historical Comparison

clinical trial

+1.2 %

Average Historical Move

Historical Analysis

Clinical trial headlines for LYEL have historically led to an average 1.23% move, with mixed direction despite consistently positive data on ronde‑cel.

Typical Pattern

Clinical updates show a steady progression from early Phase 1/2 data in LYL314/ronde‑cel to pivotal PiNACLE (3L+) and the Phase 3 head‑to‑head PiNACLE–H2H trial in 2L LBCL.

Regulatory & Risk Context

Active S-3 Shelf

Shelf Active

Active S-3 Shelf Registration 2025-12-05

An effective S-3 resale registration covers up to 1,900,000 LYEL shares held by ICT Holdings. These shares may be sold by the holder, and Lyell will not receive proceeds from such sales.

Market Pulse Summary

This announcement advances LYEL’s strategy by moving ronde‑cel into Phase 3 PiNACLE–H2H with about 4...

Analysis

This announcement advances LYEL’s strategy by moving ronde‑cel into Phase 3 PiNACLE–H2H with about 400 2L LBCL patients, while the pivotal PiNACLE 3L+ trial continues toward a planned BLA submission in 2027. Prior data showed high response rates and an outpatient‑friendly safety profile. Investors may watch enrollment pace, comparative outcomes versus liso‑cel and axi‑cel, and future regulatory filings, alongside potential effects from the 1.9M-share resale registration.

Key Terms

car t-cell, event-free survival, overall response rate, complete response rate, +4 more

8 terms

car t-cell medical

"Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of ronde-cel"

CAR T-cell therapy uses a patient’s own immune cells that have been removed, reprogrammed in a lab to recognize a specific marker on cancer cells, and returned to the body to seek and destroy tumors. Think of it as giving a person's white blood cells a custom-made 'GPS' that guides them to cancer cells. Investors watch CAR T-cell programs because they can command high prices, involve complex manufacturing and regulatory risk, and their clinical success or failure can sharply affect a biotech company's value.

event-free survival medical

"The primary endpoint of this superiority trial is event-free survival"

Event-free survival measures the length of time after a treatment or diagnosis during which a patient does not experience a predefined negative outcome, such as disease progression, relapse, or death. For investors, longer event-free survival in clinical trials signals that a therapy may be effective and durable, improving its chances of regulatory approval and commercial success — think of it like a warranty period before problems reappear.

overall response rate medical

"The primary endpoint is overall response rate."

Overall response rate is the percentage of patients in a clinical study whose measurable disease shrinks or disappears after receiving a treatment. Investors watch it like a product’s “hit rate” because higher response rates can signal a drug’s effectiveness, boost chances of regulatory approval and market demand, and affect a company’s future revenue prospects, similar to how a higher batting average suggests a more reliable player.

complete response rate medical

"including a best overall response rate of 93% and a complete response rate of 76%"

Complete response rate is the percentage of patients in a clinical trial whose measurable signs of disease disappear after treatment, as judged by predefined medical tests. For investors, a higher complete response rate is a strong signal that a drug works well in the trial setting, improving chances of regulatory approval and commercial success — like seeing most lightbulbs in a new batch actually turn on before deciding to buy the factory.

cytokine release syndrome medical

"no reports of Grade 3 or higher cytokine release syndrome (CRS)"

An intense immune overreaction in which the body's defense system releases a large surge of signaling proteins, causing fever, low blood pressure, breathing trouble or organ stress; imagine the immune system's alarm going into overdrive and flooding the body with emergency responders. Investors care because this side effect can slow or block regulatory approval, increase clinical trial costs and liabilities, limit how widely a therapy can be used, and therefore affect a drug's market value and sales potential.

immune effector cell-associated neurotoxicity syndrome medical

"one case (4%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)"

immune effector cell-associated neurotoxicity syndrome (ICANS) is a brain-related side effect that can occur after treatments that activate powerful immune cells, such as engineered cell therapies. It can cause confusion, speech problems, seizures or coma when the immune response unintentionally harms brain function; think of an overenthusiastic security system that starts damaging the house it’s protecting. Investors care because ICANS affects clinical trial results, regulatory approvals, product labeling, treatment adoption, monitoring costs and potential liability, all of which influence a therapy’s commercial value.

randomized controlled clinical trial medical

"Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of ronde-cel"

A randomized controlled clinical trial is a medical study where participants are randomly assigned to two or more groups—typically one receiving the treatment under test and another receiving a placebo or standard care—to objectively measure whether the treatment works and is safe. For investors, these trials are the gold standard for proving a drug or device’s effectiveness, because their clear, unbiased results strongly influence regulatory approval, market adoption, and the commercial value of healthcare companies.

bla submission regulatory

"pivotal single-arm trial, PiNACLE, ... with BLA submission expected in 2027"

A BLA submission is a company’s formal application to the U.S. Food and Drug Administration asking for permission to market a biologic drug or therapy. Think of it like applying for a permit to sell a complex medical product: the agency reviews safety, effectiveness, and manufacturing quality before deciding. For investors, a BLA filing signals a late-stage regulatory milestone that can reduce uncertainty and, if approved, unlock revenue and change a company’s valuation, while also carrying regulatory and timing risk.

AI-generated analysis. Not financial advice.

• PiNACLE – H2H will evaluate the efficacy and safety of rondecabtagene autoleucel (ronde-cel) versus Investigator’s choice of approved CD19 CAR T-cell therapies in patients with aggressive large B-cell lymphoma receiving treatment in the second-line setting
• The pivotal single-arm trial, PiNACLE, evaluating ronde-cel in the third- or later-line setting is ongoing with BLA submission expected in 2027
• Site activation for both PiNACLE – H2H and PiNACLE are underway in the United States, Canada and Australia
  
  

SOUTH SAN FRANCISCO, Calif., Feb. 12, 2026 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with cancer, today announced that the first patient has been dosed in the PiNACLE – H2H Phase 3 trial evaluating rondecabtagene autoleucel (ronde-cel, also known as LYL314) compared to lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) for the treatment of patients with 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, MD, 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 randomize patients between different CAR T-cell therapies.”

“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, MD, Lyell’s Chief Medical Officer. “We are now pleased to have underway PiNACLE – H2H, the first-of-its-kind Phase 3 head-to-head randomized 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.”

PiNACLE – H2H is a Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of ronde-cel versus Investigator’s choice of either liso-cel or axi-cel in patients with R/R LBCL receiving treatment in the 2L 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. The primary endpoint of this superiority trial is event-free survival and the trial plans to enroll approximately 200 patients per arm (N = 400) with R/R LBCL, including 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-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting.

More information about the PiNACLE – H2H trial can be found on clinicaltrials.gov (NCT07188558) here.

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 multi-cohort multi-center Phase 1/2 trial and will enroll approximately 120 patients at approximately 25 sites. The dose is 100 x 10⁶ CAR T cells and the primary endpoint is overall response rate. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535) here.

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 1/2 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 September 5, 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. The safety profile was appropriate for outpatient administration of ronde-cel. 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).

About Rondecabtagene Autoleucel (Ronde-cel)

Rondecabtagene autoleucel (ronde-cel, also known as LYL314) is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19-targeted CAR T-cell therapies for the treatment of R/R LBCL.

Ronde-cel is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both, each with full potency. Ronde-cel 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.

Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) designation as well as Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of adults with R/R diffuse LBCL (DLBCL) in the 3L+ setting and has also received RMAT designation for the treatment of LBCL in the 2L setting. The FDA has also granted ronde-cel Orphan Drug Designation for the treatment of DLBCL/high grade B-cell lymphoma with MYC and BCL2 rearrangements.

About Lyell

Lyell is a clinical stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with hematologic malignancies and solid tumors. To realize the potential of cell therapy for cancer, Lyell utilizes a suite of technologies to arm CAR T cells with enhancements needed to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness, and function in the hostile tumor microenvironment. Lyell’s LyFE Manufacturing Center™ has commercial launch capability and can manufacture more than 1,200 CAR T-cell doses at full capacity. To learn more, please visit www.lyell.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: the potential clinical benefits and therapeutic potential of ronde-cel; Lyell’s expectations around the progress of the PiNACLE and PiNACLE – H2H trials, including expectations around enrollment, and the timing of regulatory submissions for ronde-cel; the sufficiency of the capacity of LyFE to manufacture drug supply through potential commercial launch; and other statements that are not historical fact. These statements are based on Lyell’s current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: Lyell’s limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; the nonclinical profiles of Lyell’s product candidates or technology not translating in clinical trials; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; the potential for interim results from a clinical trial as of a data cutoff to not be necessarily indicative of final results and for one or more of the clinical and safety outcomes to materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient or final data become available; significant adverse events, toxicities or other undesirable side effects associated with Lyell’s product candidates, including the risk that the ultimate safety profile of ronde-cel may not support outpatient administration; Lyell’s ability to submit planned regulatory submissions or initiate or progress clinical trials on the anticipated timelines, if at all; RMAT and Fast Track designations may not actually lead to faster development, regulatory review or approval process, and do not assure ultimate FDA approval; the significant uncertainty associated with Lyell’s product candidates ever receiving any regulatory approvals; the complexity of manufacturing cellular therapies and Lyell’s ability to manufacture and supply its product candidates for its clinical trials; implementation of Lyell’s strategic plans, and Lyell’s realization of the expected benefits of such plans, for its business and product candidates; the sufficiency of Lyell’s capital resources and need for additional capital to achieve its goals; and other risks, including those described under the heading “Risk Factors” in Lyell’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the U.S. Securities and Exchange Commission on November 12, 2025. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law.

Contact:

Peter Tran
Senior Director, Finance
ptran@lyell.com

FAQ

What is the design of Lyell's PiNACLE – H2H Phase 3 trial (LYEL)?

It's a randomized head-to-head Phase 3 trial comparing ronde-cel to liso-cel or axi-cel. According to the company, the superiority trial will enroll ~400 patients with event-free survival as the primary endpoint.

What efficacy did Lyell report for ronde-cel in aggressive LBCL at ASH 2025?

Ronde-cel showed a 93% best overall response rate and 76% complete response rate in the 3L+ cohort. According to the company, these results come from 29 efficacy-evaluable patients with median PFS of 18 months.

How many patients will PiNACLE – H2H enroll and what is the dosing for ronde-cel?

PiNACLE – H2H plans to enroll approximately 400 patients total, ~200 per arm. According to the company, ronde-cel dose is 100 x 10^6 CAR T cells; control arm follows product label dosing.

When does Lyell expect to seek FDA approval for ronde-cel (LYEL)?

Lyell expects to submit a BLA for the pivotal 3L+ PiNACLE trial in 2027. According to the company, the single-arm registration trial is ongoing and forms the basis for the filing timeline.

What safety results were reported for ronde-cel in the presented data?

Safety was described as appropriate for outpatient use with no Grade 3+ CRS reported. According to the company, one case (4%) of Grade 3+ ICANS was observed among 25 patients on dexamethasone prophylaxis.

Where and when are PiNACLE and PiNACLE – H2H being conducted (LYEL)?

Site activation is underway in the United States, Canada and Australia for both trials. According to the company, the first PiNACLE – H2H patient was dosed on February 12, 2026.