Galapagos NV announced encouraging new data from its ongoing Phase 1/2 ATALANTA-1 study of GLPG5101, a CD19 CAR T-cell therapy, in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). The results, presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, showcase promising efficacy and safety, along with the feasibility of rapid decentralized manufacturing.
The ATALANTA-1 study (EudraCT 2021-003272-13) is an open-label, multicenter trial evaluating the safety, efficacy, and feasibility of decentralized manufacturing of GLPG5101 in R/R NHL patients. GLPG5101 is a second-generation anti-CD19/4-1BB CAR-T product administered as a single fixed intravenous dose. The study included patients with mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).
High Response Rates Across NHL Subtypes
As of the April 25, 2024, data cut-off, 49 patients received GLPG5101, with efficacy results available for 42 patients. The data revealed high objective response rates (ORR) and complete response rates (CRR) across various NHL subtypes:
- Mantle Cell Lymphoma (MCL): 100% ORR and CRR (8 of 8 patients).
- Marginal Zone Lymphoma (MZL) and Follicular Lymphoma (FL): 95% ORR and CRR (20 of 21 patients).
- Diffuse Large B-Cell Lymphoma (DLBCL): 69% ORR (9 of 13 patients), with 54% CRR (7 of 13 patients). In the higher dose cohort, ORR was 86% and CRR was 71%.
Of the 15 minimal residual disease (MRD)-evaluable patients with a complete response, 80% achieved MRD negativity and remained in complete response at the data cut-off.
Rapid Vein-to-Vein Time
A key highlight of the study was the rapid manufacturing and delivery of GLPG5101. 96% of patients received an infusion of fresh, fit, stem-like early memory CD19 CAR T-cells, with 91.5% achieving a median vein-to-vein time of seven days. This rapid turnaround avoids the need for cryopreservation and bridging therapy, potentially benefiting patients with aggressive lymphomas where treatment delays can be detrimental.
Marie José Kersten, MD, ATALANTA-1 Principal Investigator and Professor of Hematology at Amsterdam University Medical Center, noted, "Shorter vein-to-vein time can lead to improved patient outcomes and remains an important unmet need in CAR-T therapy... With a median vein-to-vein time of just seven days, GLPG5101 has the potential to offer speed and scheduling flexibility, comparable to off-the-shelf therapies."
Safety Profile
GLPG5101 demonstrated an encouraging safety profile. The majority of Grade ≥ 3 treatment-emergent adverse events were hematological. One case of Grade 3 cytokine release syndrome (CRS) was observed in Phase 1, and one case of Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in Phase 2.
Decentralized Manufacturing Platform
Galapagos' decentralized cell therapy manufacturing platform is designed to enable the administration of fresh, fit, stem-like, early memory T-cells with greater physician visibility and improved patient experience. The platform includes the xCellit® workflow management and monitoring software system, a functionally closed, automated manufacturing platform (using Lonza’s Cocoon®), and a proprietary quality control testing and release strategy.
Jeevan Shetty, MD, Head of Clinical Development Oncology at Galapagos, stated, "Our latest data at ASH strongly support the feasibility of our innovative decentralized cell therapy manufacturing platform in delivering fresh, fit cells with a median vein-to-vein time of just seven days, driving positive patient outcomes."
