Galapagos Cleared by FDA to Bring Trial for CAR-T Therapy GLPG5101 in R/R NHL to US

Jeevan Shetty, MD
Credit: Galapagos

Galapagos has received clearance from the FDA of an investigational new drug (IND) application for GLPG5101, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, allowing the company to evaluate the CAR-T for the treatment of relapsed/refractory (r/r) nonHodgkin lymphoma (NHL) in a phase 1/2 clinical trial.¹

In light of the IND application,Galpagos intends to bring its phase 1/2 ATALANTA-1 clinical trial (NCT06561425), which is currently ongoing in Europe, to the United States. The phase 1 portion of the trial is focused on safety, preliminary efficacy, and finding the recommended dose for the phase 2 portion, with secondary end points covering feasibility of decentralized manufacturing for the CAR-T product. The phase 2 portion of ATALANTA-1 will utilize objective response rate as the primary end point with secondary end points covering complete response (CR) rate, duration of response, progression-free survival, overall survival, safety, the pharmacokinetic profile, and the feasibility of decentralized manufacturing. The open-label, multicenter trial will follow patients for 24 months posttreatment.

According to the clinicaltrials.gov page, which was most recently updated on August 20, 2024, ATALANTA-1 is currently recruiting patients at some locations in Belgium and the Netherlands, and has sites in Boston, Massachusetts that are not yet recruiting. Notably, GLPG5101 is an autologous CAR-T therapy that is expected to be able to be manufactured with a median vein-to-vein time of 7 days.

“We are dedicated to accelerating breakthrough innovation that extends the reach of cell therapies to patients with rapidly progressing cancers,” Paul Stoffels, MD, the chief executive officer and chairman of the board of directors at Galapagos, said in a statement.¹ “Our innovative, decentralized manufacturing platform is designed to overcome many of the challenges faced by existing CAR-T production methods. The Galapagos platform has the potential for greater speed and scalability, with the delivery of fresh, fit cells with a median vein-to-vein time of 7 days, close to patients. The IND clearance for the phase 1/2 study of GLPG5101 marks a significant milestone in our cell therapy clinical program, bringing us one step closer to offering our CD19 CAR-T cell therapy to patients in the US.”

The company recently presented early data from European participants in ATALANTA-1 at the European Hematology Association (EHA) 2024 Congress, held June 13 to 16, both virtually and in Madrid, Spain.² It was reported that 14 of 16 patients (87.5%) evaluable for efficacy in phase 1 responded to the CAR-T and that 12 of these patients (75%) achieved a CR. Fourteen of 15 patients (93.3%) in the phase 2 portion who were evaluable for efficacy achieved a response, and all these responses were CRs. In terms of safety, there were 2 cases of grade 3 cytokine release syndrome (CRS) in the phase 1 portion and 1 case of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) reported in the phase 2 portion. The safety profile was characterized as “encouraging”, with the company pointing out that the majority of adverse events assessed as grade 3 or greater were hematological in nature.

“We are committed to accelerating breakthrough innovations to extend the reach of CAR-T therapies to patients with rapidly progressing cancers,” Jeevan Shetty, MD, the head of clinical development oncology at Galapagos, said in a statement at the time.² “We are delighted to present promising new data for GLPG5101 at the EHA congress. The high CR rates, combined with low-grade CRS and ICANS, demonstrates the potential of GLPG5101 in addressing the critical needs of this patient population. The data also confirm the feasibility of our innovative decentralized T-cell manufacturing platform in delivering fresh, fit cells with a median vein-to-vein time of just 7 days.”

REFERENCES
1. Galapagos announces FDA clearance of IND application for phase 1/2 ATALANTA-1 study of CD19 CAR-T, GLPG5101, in relapsed/refractory non-Hodgkin lymphoma. News release. Galapagos NV. August 23, 2024. Accessed August 26, 2024. https://www.glpg.com/press-releases/galapagos-announces-fda-clearance-of-ind-application-for-phase-1-2-atalanta-1-study-of-cd19-car-t-glpg5101-in-relapsed-refractory-non-hodgkin-lymphoma/
2. Galapagos presents encouraging new data for CD19 CAR-T candidate GLPG5101 in non-Hodgkin lymphoma at EHA 2024. News release. Galapagos NV. June 14, 2024. Accessed August 26, 2024. https://www.glpg.com/press-releases/galapagos-presents-encouraging-new-data-for-cd19-car-t-candidate-glpg5101-in-non-hodgkin-lymphoma-at-eha-2024/