Core Insights - Lyell Immunopharma, Inc. announced new clinical data for its CAR T-cell therapy, ronde-cel, showing promising efficacy in treating large B-cell lymphoma (LBCL) with a 93% overall response rate and a 76% complete response rate in the 3L+ setting [1][5][12] - Ronde-cel has received FDA Regenerative Medicine Advanced Therapy (RMAT) designation, indicating its potential as a significant treatment option for patients with relapsed and/or refractory LBCL [2][17] Clinical Data Summary - In the 3L+ setting, 29 patients showed a 93% overall response rate and a 76% complete response rate, with a median progression-free survival of 18 months [4][5] - In the 2L setting, 18 patients, predominantly with primary refractory disease, achieved an 83% overall response rate and a 61% complete response rate [6][12] - Safety profile was manageable, with no high-grade cytokine release syndrome (CRS) and low rates of Grade 1 (32%) and Grade 2 (29%) CRS reported [7][6] Pivotal Trials - Lyell has initiated two pivotal trials: PiNACLE – H2H, a head-to-head trial comparing ronde-cel to other CAR T-cell therapies, and PiNACLE, a single-arm trial for the 3L+ setting [8][10] - The PiNACLE – H2H trial aims to enroll approximately 400 patients and focuses on event-free survival as the primary endpoint [9] Translational Data - Ronde-cel demonstrated robust expansion and high expression of memory-related genes post-infusion, with a higher proportion of CD62L-positive T cells compared to other CAR T-cell products [11] - The product showed up to a three-fold higher expansion in patients after infusion compared to approved CD19 CAR T-cell products [11] Company Overview - Lyell Immunopharma is focused on advancing next-generation CAR T-cell therapies for hematologic malignancies and solid tumors, utilizing proprietary manufacturing processes to enhance T-cell efficacy [18][16]

Core Viewpoint - Lyell Immunopharma has initiated the PiNACLE - H2H Phase 3 trial to evaluate its dual-targeting CAR T-cell therapy, rondecabtagene autoleucel (ronde-cel), against existing CD19-targeting therapies for relapsed or refractory large B-cell lymphoma [1][10] Group 1: Trial Details - The PiNACLE - H2H trial is a head-to-head randomized controlled trial comparing ronde-cel to either lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B-cell lymphoma [1][10] - The trial aims to enroll approximately 400 patients and will assess event-free survival as the primary endpoint [10] - Ronde-cel is designed to target B cells expressing either CD19, CD20, or both, with a focus on improving complete response rates and duration of responses compared to existing therapies [5][6] Group 2: Product Information - Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the FDA for the treatment of patients with relapsed or refractory large B-cell lymphoma [7] - The manufacturing process of ronde-cel aims to produce a higher proportion of naïve and central memory T cells, enhancing its antitumor activity [6][8] - The company is also conducting a single-arm pivotal trial (PiNACLE) for ronde-cel in the third-line or later setting, expected to enroll around 120 patients [10] Group 3: Expert Collaboration - A Steering Committee of distinguished lymphoma experts has been established to guide the trial's design and execution [2][3] - Experts involved include members from prominent institutions such as the University of Chicago and the Moffitt Cancer Center [4][10] - The collaboration aims to provide robust clinical data to support the potential benefits of ronde-cel over existing therapies [2][3]