Rondecabtagene autoleucel, an autologous, dual-targeting CD19/CD20 CAR T-cell candidate manufactured from CD62L+ enriched T cells, achieves durable responses in patients with large B-cell lymphoma
Year: 2025
Type: conference-abstract
Abstract: Background: Single-antigen CD19-targeting chimeric antigen receptor (CAR) T-cell therapies have become a standard of care for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), yet opportunity remains to improve outcomes. Rondecabtagene autoleucel (ronde-cel, LYL314) is an autologous, dual-targeting CD19/CD20 CAR T-cell product candidate manufactured from CD62L+ enriched naïve and central memory T cells. Ronde-cel is designed to maximize response regardless of baseline antigen heterogeneity, while reducing CAR T-cell exhaustion, enhancing T-cell persistence, and mitigating antigen loss. Here, we present updated data from the ongoing Phase 1/2 multi-center trial (NCT05826535) with a focus on patients with high-risk second-line (2L) LBCL, as well as extended follow up of patients treated in the third- or later-line (3L+) setting. Enrollment is ongoing and additional data will be available at the time of the conference. Methods: Patients with R/R disease that was measurable prior to lymphodepletion (LD) were enrolled, patients treated in a 2L setting were required to have relapsed within 12 months of first-line therapy or had primary refractory disease. No baseline CD19 or CD20 antigen testing was required for enrollment and there was no upper age limit. Following a standard 3-day LD regimen of fludarabine and cyclophosphamide, patients received a single dose of ronde-cel, in the outpatient or inpatient setting, at the recommended Phase 2 dose (RP2D) of 100 x 106 CAR cells. The primary endpoint is overall response rate, and key secondary endpoints include CR rate, progression free survival and pharmacokinetics. Results: As of June 27, 2025, 60 patients had received ronde-cel (23 2L; 37 3L+). Median age was 65 years (range 21-87), 65% (39/60) had ECOG status of 1, 40% (24/60) had an International Prognostic Index of ≥ 3 at time of enrollment, 55% (33/60) had Stage IV disease, 42% (25/60) had elevated lactate dehydrogenase (LDH) at baseline, and 55% (33/60) received bridging therapy. Median (IQR) baseline tumor burden (sum of target lesion product diameters) was 18.2 cm2 (6 - 42). In the 2L setting, 70% (16/23) of patients had primary refractory disease. Forty-six patients were response evaluable: 15 and 31 in the 2L and 3L+ settings, with median follow up of 7 and 10 months, respectively. Among patients in the 2L, the overall response rate was 87% (13/15) including a complete response rate of 60% (9/15), with 100% (7/7) of patients with complete response remaining in complete response at ≥ 6 months. Among the patients in 3L+, the overall response rate was 90% (28/31) and the complete response rate was 71% (22/31). Grade 1 or 2 cytokine release syndrome (CRS) was reported in 62% (37/60) patients, with no ≥ Grade 3 CRS, and 42% (25/60) of all patients receiving tocilizumab. Grade 1 or 2 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 12% (7/60) of patients. Grade ≥ 3 ICANS was reported in 13% (8/60) of patients, including 7% (1/15) of patients after the introduction of routine dexamethasone prophylaxis, and resolved promptly with standard therapy (median time to < Grade 3 was 2.5 days). Grade 3 infections were reported in 13% (8/60) patients. There were no deaths on study related to ronde-cel. Conclusions: Ronde-cel achieved high overall response and complete response rates with an encouraging safety profile in high-risk patients with LBCL in a Phase 1/2 multi-center trial. Complete responses were durable, including 100% CR at ≥ 6 months among patients treated in the 2L setting. A single-arm pivotal trial of ronde-cel is ongoing in patients treated in the 3L+ setting (PiNACLE), and a Phase 3 head-to-head, randomized controlled trial of ronde-cel versus investigator's choice of approved CD19 CAR T-cell therapy (lisocabtagene maraleucel or axicabtagene ciloautoleucel) has been initiated (PiNACLE-H2H).
Source: Blood
Authors: Sarah Larson, Umar Farooq, Tahir Latif, Felix Mensah, Bradley Hunter, Stefan Ciurea, Nebu Koshy, Locke Bryan, Boyu Hu, William Clark, Hassaan Yasin, Yeonhee Kim, Greg Kaufman, Akil Merchant
Institutions: University of California, Los Angeles, Ronald Reagan UCLA Medical Center, University of Iowa, University of Cincinnati, University of Cincinnati Medical Center, Franciscan Health Indianapolis, Intermountain Healthcare, University of California, Irvine, Baylor Scott & White Health, Augusta University, University of Utah, Huntsman Cancer Institute, Virginia Commonwealth University, University of Louisville, Lyell Immunopharma (United States), Cedars-Sinai Medical Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417007997