Lyell's Ronde-cel Shows 93% Response Rate in Large B-Cell Lymphoma with Enhanced Safety Profile
核心洞察
Ronde-cel (搜索) demonstrated a 93% overall response rate and 76% complete response rate with 18-month median progression-free survival in third-line or later large B-cell lymphoma (搜索) patients.
The dual-targeting CD19 (搜索)/CD20 (搜索) CAR T-cell therapy achieved an 83% overall response rate in second-line patients, with 94% having primary refractory disease.
Safety profile showed no high-grade cytokine release syndrome and only 5% of patients experienced Grade 3 or higher immune effector cell-associated neurotoxicity syndrome.
Lyell Immunopharma presented compelling new clinical data for rondecabtagene autoleucel (搜索) (ronde-cel (搜索)) at the 67th American Society of Hematology Annual Meeting, demonstrating exceptional efficacy rates in patients with relapsed/refractory large B-cell lymphoma (搜索) (LBCL). The dual-targeting CD19 (搜索)/CD20 (搜索) CAR T-cell therapy achieved a 93% overall response rate and 76% complete response rate in the third-line or later setting, with a median progression-free survival of 18 months as of the September 5, 2025 data cutoff.
Strong Efficacy Across Treatment Lines
In the third-line or later (3L+) setting, 29 efficacy-evaluable patients with relapsed/refractory LBCL showed remarkable responses. The 93% overall response rate included 76% of patients achieving complete responses, with 72% of complete responders maintaining their response at six months or longer. The median progression-free survival reached 18 months, representing a significant milestone for this heavily pretreated population.
Second-line (2L) patients, comprising predominantly those with primary refractory disease (94%), demonstrated an 83% overall response rate with 61% achieving complete responses. Notably, 70% of patients with complete responses remained in remission at six months or longer, with the median duration of complete response not yet reached.
The study population represented a high-risk cohort with challenging disease characteristics. Median patient ages were 64-65 years, with approximately 20% of patients being 75 years or older. Primary refractory disease was present in 49% of 3L+ patients and 92% of 2L patients, indicating a particularly difficult-to-treat population compared to historical CAR T-cell trials.
Enhanced Safety Profile Enables Outpatient Treatment
Ronde-cel (搜索) demonstrated a manageable safety profile across 69 treated patients that supports outpatient administration. No Grade 3 or higher cytokine release syndrome (CRS) was observed in any patient. Among the 25 patients who received protocol-directed dexamethasone prophylaxis (10 mg/day for three days), only one case (4%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.
Overall safety rates showed low-grade toxicities: Grade 1 CRS in 32% and Grade 2 CRS in 29% of patients. ICANS occurred as Grade 1 in 9%, Grade 2 in 3%, and Grade 3 or higher in 12% of patients. The median time to complete resolution of ICANS was four days. Importantly, no deaths were attributed to ronde-cel (搜索) administration.
Innovative Manufacturing Process Drives Performance
Ronde-cel (搜索)'s enhanced performance stems from its proprietary manufacturing process that enriches for CD62L (搜索)-positive cells, producing a CAR T-cell product with higher proportions of naïve and central memory T cells. Translational data revealed that ronde-cel achieved up to three-fold higher expansion in patients compared to approved CD19 (搜索) CAR T-cell products.
The therapy utilizes an 'OR' logic gate design to target B cells expressing either CD19 (搜索), CD20 (搜索), or both antigens with full potency. This dual-targeting approach is designed to increase complete response rates and prolong response duration compared to single-target CD19 CAR T-cell therapies.
Pivotal Trial Program Advances
Lyell has initiated two pivotal clinical trials for ronde-cel (搜索). The PiNACLE – H2H Phase 3 trial represents the first head-to-head CAR T-cell comparison, randomizing approximately 400 patients to receive either ronde-cel or investigator's choice of lisocabtagene maraleucel or axicabtagene ciloleucel in the second-line setting. The primary endpoint is event-free survival.
The single-arm PiNACLE trial is enrolling up to 120 patients in the 3L+ setting, with overall response rate as the primary endpoint. Both trials allow for inpatient or outpatient treatment administration.
"These data from the ongoing clinical trial showing high rates of durable complete responses along with a manageable safety profile in patients with high-risk large B-cell lymphoma (搜索) represent the potential of ronde-cel (搜索) to improve patient outcomes," commented Sarah M. Larson, MD, Associate Professor at UCLA's David Geffen School of Medicine (搜索). "The two pivotal trials underway, including the first-of-its kind head-to-head CAR T-cell trial, are expected to provide a comprehensive and robust evaluation of the potential for ronde-cel to demonstrate differentiated benefit over approved CD19 (搜索) CAR T-cell therapies."
The FDA has granted ronde-cel (搜索) Regenerative Medicine Advanced Therapy designation for both 3L+ and 2L settings, along with Fast Track Designation for the 3L+ indication, potentially accelerating the regulatory pathway for this promising therapy.