Paper Details

ABSTRACT

Background: Single-antigen CD19-targeted CAR T-cell therapies are part of routine care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, opportunity remains to improve response depth and durability, particularly in the third- or later-line (3L+) setting where the overall response rate (ORR) is 72–73%, the complete response rate (CRR) is 51–54%, and the median progression-free survival (mPFS) is 6–7 months in FDA-approved CAR-T products. Rondecabtagene autoleucel (ronde-cel) is a next-generation, 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 B-cell targeting regardless of baseline antigen heterogeneity, enhance?T-cell functional persistence, and improve durability of response. Here we report data from the ongoing pivotal PiNACLE trial in 3L+ R/R LBCL (NCT05826535). 

Methods: PiNACLE is a pivotal, multicenter, open-label, single-arm trial enrolling CAR-naïve patients with R/R LBCL who have received ≥ 2 prior lines of therapy, including an anti-CD20 antibody and an anthracycline. Following leukapheresis and optional bridging therapy, patients received lymphodepletion and a single ronde-cel infusion. Imaging assessments were reported using Lugano 2014 criteria as determined by the site investigator. The primary endpoint of the pivotal trial is ORR. Safety was graded per CTCAE v5.0, with cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) graded per ASTCT criteria. Safety was assessed in all patients who received ronde-cel; efficacy was assessed in patients with evaluable scans at Day 84 or who had earlier disease progression or death prior to Day 84. 

Results: Fifty-eight CAR-naïve patients with 3L+ R/R LBCL received ronde-cel (as of 18 June 2026). Median age was 64 years (range, 28–86); 71% were male and 79% were White. Fifty percent had primary refractory disease and 64% were refractory to their last line of therapy. 69% had DLBCL and 9% had double- or triple-hit lymphoma. At baseline, 67% had Stage III/IV disease, 38% had elevated lactate dehydrogenase, and 47% received bridging therapy.  

Of these, 44 patients were response-evaluable at Day 84. The ORR was 91% (40/44; 95% CI, 78–97), with a CRR of 77% (34/44; 95% CI, 62–89). Among the 34 patients achieving CR, median duration of complete response (DoCR) was not reached (95% CI: 9.1, NR), with estimated continued CR of 92% at 6 months and 75% at 12 months. Median PFS was not reached (95% CI: 9.0, NR), with PFS rates of 76%, 63%, and 54% at 6, 12, and 24 months, respectively. Median PFS follow-up was 12 months.  

No Grade ≥ 3 CRS was observed among all treated patients (N = 58). CRS occurred in 71% (41/58), all Grade 1 (48%) or Grade 2 (22%). Median time to CRS onset was 5 days, with a median time to resolution of 3 days (range, 1–13). ICANS occurred in 26% (15/58), including Grade ≥ 3 in 9% (5/58). Median time to ICANS onset was 7 days, with a median time to resolution of 1 day (range, 1–11). One Grade 2 IEC-HS event was observed (2%, 1/58). The most common Grade ≥ 3 treatment-emergent adverse events were cytopenias (neutropenia 45%, thrombocytopenia 21%, anemia 16%); Grade ≥ 3 infections occurred in 7% (4/58). There were no deaths related to ronde-cel.   

Conclusion: Ronde-cel achieved a high complete response rate (77%) and durable responses, with median PFS not reached and continued CR of 75% at 12 months, in patients with 3L+ R/R LBCL. Responses were observed in over 90% of patients. The safety profile was manageable, with no Grade ≥ 3 CRS, supporting outpatient administration in the ongoing pivotal trial. Updated results, including additional patients and longer follow-up, will be presented.