Galapagos unveils promising data for CD19 CAR-T GLPG5101 in non-Hodgkin lymphoma at EHA 2024

On June 14, 2024, Galapagos NV (Euronext & NASDAQ: GLPG) announced significant updates regarding their Phase 1/2 ATALANTA-1 study for the CD19 CAR-T candidate, GLPG5101, in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). The findings were presented at the European Hematology Association (EHA) 2024 Hybrid Congress.

The ATALANTA-1 study focuses on different subtypes of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). The study aims to evaluate both the safety and efficacy of GLPG5101, which is produced using Galapagos’ innovative decentralized T-cell manufacturing platform. This unique platform ensures a median vein-to-vein time of just seven days, allowing for the administration of fresh CAR-T cells in 94% of patients without the need for bridging therapy.

Key findings from the ATALANTA-1 study, as of December 20, 2023, reveal that GLPG5101 has a promising safety profile. Most treatment-emergent adverse events (TEAEs) were Grade 1 or 2, with only a few Grade 3 events, primarily hematological. Specifically, two cases of Grade 3 cytokine release syndrome (CRS) were observed in Phase 1, and one case of Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was noted in Phase 2.

In terms of efficacy, results were encouraging. In Phase 1, 14 out of 16 efficacy-evaluable patients responded to the treatment, achieving an objective response rate (ORR) of 87.5%, with 12 patients showing a complete response (CR) (CR rate of 75%). Phase 2 showed even better results, with all 14 efficacy-evaluable patients responding (ORR of 93.3%) and achieving complete response (CR rate of 93.3%).

The pooled data from both phases showed high ORR and CRR across different lymphoma subtypes. For DLBCL, 7 out of 9 efficacy-evaluable patients responded to treatment (ORR of 78%), with 5 achieving a complete response (CRR of 56%). In FL and MZL patients, 16 out of 17 efficacy-evaluable patients responded (ORR and CRR of 94%). All 5 MCL patients achieved both an objective and complete response (ORR and CRR of 100%).

Durability of the response was also impressive. In Phase 1, 71% of the responding patients maintained their response with a median follow-up of 13.1 months. In Phase 2, all patients had an ongoing response at the data cut-off date, with a median follow-up of 4.2 months. Moreover, strong and consistent CAR-T cell expansion was observed in vivo, indicating effective cellular kinetics.

Dr. Marie José Kersten, Professor of Hematology and Head of the Department of Hematology at the Amsterdam University Medical Center, presented these findings. Dr. Jeevan Shetty, Head of Clinical Development Oncology at Galapagos, emphasized the company's commitment to advancing CAR-T therapies for patients with rapidly progressing cancers. He highlighted that the high complete response rates, combined with low-grade CRS and ICANS, underscore the potential of GLPG5101 to address critical patient needs.

The ATALANTA-1 study is structured to evaluate the safety, efficacy, and feasibility of GLPG5101, administered as a single fixed intravenous dose. In Phase 1, dose levels of 50×10^6, 110×10^6, and 250×10^6 CAR+ viable T cells were assessed to determine the recommended dose for Phase 2. The primary objective of Phase 2 is to evaluate the objective response rate (ORR), while secondary objectives include complete response rate (CRR), duration of response, progression-free survival, overall survival, safety, and pharmacokinetic profile.

Non-Hodgkin lymphoma, the focus of this study, originates from lymphocytes and can present aggressive or indolent forms. The prognosis and treatment vary depending on the type and stage of the disease. Galapagos' decentralized T-cell manufacturing platform aims to revolutionize treatment, offering high-quality CAR-T cells within a short timeframe, improving both physician control and patient outcomes.

In conclusion, the latest data from the ATALANTA-1 study highlights the potential of GLPG5101 as a transformative treatment for patients with relapsed/refractory non-Hodgkin lymphoma, supported by the innovative decentralized manufacturing approach of Galapagos.