Phase I/II ATALANTA-1 study: Dose escalation of GLPG5101 for R/R B-cell NHL

Results from the dose escalation of the single-arm, multicenter, phase I/II ATALANTA-1 study (NCT06561425), evaluating GLPG5101, an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy, in 24 adults with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma [DLBCL], n = 17; follicular lymphoma [FL] or marginal zone lymphoma [MZL], n = 4; mantle cell lymphoma [MCL], n = 3), were published in The Lancet Haematology by Kersten et al. GLPG5101 was manufactured on a decentralized platform, with a target vein-to-vein time of 7 days. The planned dose levels were 35–50 × 10⁶ viable CAR⁺ T cells (dose level 1), 85–110 × 10⁶ viable CAR⁺ T cells (dose level 2), and 200–250 × 10⁶ viable CAR⁺ T cells (dose level 3). The primary endpoints were safety and determination of the recommended phase II dose (RP2D).

Key data: One patient received a non-conforming product, while the remaining patients received less than dose level 1 (n = 1), dose level 1 (n = 7), dose level 2 (n = 12), or dose level 3 (n = 3). In the 14-week treatment period, all patients included in the safety analysis population (n = 23) had Grade ≥3 treatment-emergent adverse events (TEAEs); the most common were neutropenia (96%), leukopenia (39%), lymphopenia (30%), anemia (26%), and thrombocytopenia (22%). Cytokine release syndrome (CRS) occurred in 48% of patients and was Grade 1–2 in all but one case; immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 30% and was exclusively Grade 1. Overall, five dose-limiting toxicity (DLT) events were reported: Grade 3 thrombocytopenia (dose level 1, n = 1), death from intra-abdominal hemorrhage (dose level 2, n = 1), Grade 4 prolonged neutropenia (dose level 1, n = 1; dose level 2, n = 2). Treatment-related deaths occurred in four patients. The objective response rate (ORR) across 22 evaluable patients was 86% (95% confidence interval [CI], 65.1–97.1), including a complete response (CR) rate of 77%. The safety review committee selected 110 × 10⁶ (range 50–110 × 10⁶) viable CAR T cells as the recommended phase II dose.

Key learning: Results from the ATALANTA-1 study demonstrate the feasibility of rapid, decentralized GLPG5101 manufacturing, with high response rates in patients with R/R B-cell NHL.