South San Francisco, CA - Lyell Immunopharma, Inc. (Nasdaq: LYEL) has announced the initiation of PiNACLE-H2H, a Phase 3 head-to-head clinical trial evaluating its next-generation CAR T-cell therapy, rondecabtagene autoleucel (ronde-cel), against existing CD19 CAR T-cell therapies for relapsed or refractory large B-cell lymphoma (R/R LBCL). This trial marks a significant milestone in the field of immunotherapy, aiming to redefine treatment paradigms for aggressive lymphomas.

The Innovation Behind Ronde-cel

Ronde-cel is a dual-targeting CAR T-cell therapy designed to address limitations of current CD19-only therapies. By targeting both CD19 and CD20 antigens, ronde-cel aims to overcome antigen escape--a mechanism by which cancer cells evade treatment by downregulating CD19 expression. Additionally, the therapy is manufactured to enrich for naive and central memory T cells, which are associated with enhanced antitumor activity and longer-lasting responses.

Dr. David Shook, Lyell's Chief Medical Officer, emphasized the potential of ronde-cel: "Targeting both CD19 and CD20 with full potency can deliver more complete responses and prolong remission compared to single antigen-targeting therapies."

The PiNACLE-H2H Trial

The trial will enroll approximately 400 patients with R/R LBCL in the second-line treatment setting. Participants will be randomized to receive either ronde-cel or an investigator's choice of approved CD19 CAR T-cell therapies, such as lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel). The primary endpoint is event-free survival, with patient enrollment expected to begin in early 2026.

Notably, ronde-cel offers flexibility for both inpatient and outpatient administration, with a 14-day monitoring period near the treatment center. This logistical advantage could make the therapy more accessible to patients.

Expert Steering Committee

To guide the trial, Lyell has assembled a distinguished Steering Committee comprising leading lymphoma and cell therapy experts, including:

• Dr. Michael Bishop, University of Chicago
• Dr. Michael Jain, Moffitt Cancer Center
• Dr. Manali Kamdar, University of Colorado
• Dr. Matthew Lunning, University of Nebraska Medical Center
• Dr. Krish Patel, Sarah Cannon Research Institute
• Dr. Jason Westin, MD Anderson Cancer Center

Dr. Jain expressed optimism about ronde-cel's potential: "The promising data from the Phase 1/2 trial suggest this innovative therapy can improve clinical outcomes for patients."

Implications for Patients

For patients with relapsed or refractory LBCL, the PiNACLE-H2H trial represents hope for improved outcomes. Current CD19 CAR T-cell therapies have shown efficacy but are limited by issues like antigen escape and durability of response. Ronde-cel's dual-targeting mechanism and enhanced manufacturing process aim to address these challenges, potentially setting a new standard in CAR T-cell therapy.

Dr. Matthew Lunning highlighted the trial's comprehensive design: "We've included a broad spectrum of patients and designed the trial to provide robust data on ronde-cel's clinical benefits."

Lyell's Strategic Vision

Lyell's approach to advancing CAR T-cell therapies is underpinned by its proprietary technologies and manufacturing capabilities. The company's LyFE Manufacturing Center can produce over 1,200 CAR T-cell doses annually, ensuring scalability for commercial launch.

With regulatory designations like RMAT and Fast Track from the FDA, Lyell is well-positioned to accelerate ronde-cel's development. The company is also conducting a parallel single-arm pivotal trial (PiNACLE) for third-line-plus LBCL treatment, further demonstrating its commitment to addressing unmet needs in oncology.

The PiNACLE-H2H trial is a bold step forward in the fight against aggressive lymphomas. By directly comparing ronde-cel to existing therapies, Lyell aims to provide compelling evidence of its dual-targeting CAR T-cell therapy's superiority. For patients and clinicians alike, this trial could herald a new era in cancer treatment, offering hope for more durable and effective solutions.

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 CD19â?'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 naive 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 anti-tumor activity. Ronde-cel has received RMAT designation, as well as Fast Track Designation, from the FDA for the treatment of patients with R/R LBCL in the 3L+ setting.

About Lyell

Lyell is a late-stage clinical 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 endow CAR T cells with attributes 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(TM) 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.

 

 

The post Lyell Immunopharma Launches Groundbreaking Phase 3 Trial for Dual-Targeting CAR T-Cell Therapy in Aggressive Large B-Cell Lymphoma appeared first on PRISM MarketView.

COMTEX_468517634/2927/2025-09-03T08:30:25