FDA Grants RMAT Status to Novel CAR-T GLPG5101 for Mantle Cell Lymphoma

The FDA has granted GLPG5101 a Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL), according to Galapagos NV, the developer of the investigational, second-generation anti-CD19/4-1BB CAR T-cell therapy.¹

The RMAT designation was based on data from the phase 1/2 ATALANTA-1 trial. Findings from the trial presented at the 2024 American Society of Hematology Annual Meeting showed a 100% complete response (CR) rate among patients with MCL, with all 8 efficacy-evaluable patients achieving a CR.² Further, 2 patients who achieved a CR also reached minimal residual disease negativity.

RMAT status gives Galapagos NV several advantages intended to expedite the development and regulatory review of GLPG5101, including increased communication with the FDA and eligibility for accelerated approval.

“This designation reflects the promising clinical activity and safety profile observed in our ongoing phase 1/2 study and supports our commitment to delivering an effective and timely treatment option to patients in need,” Omotayo Fasan, MD, clinical development program head at Galapagos, stated in a press release.¹ “With RMAT status allowing for closer collaboration with the FDA, this will enable additional opportunities for accelerated development and assessment timelines.”

Additional ATALANTA-1 Data

The latest safety data from the ATALANTA-1 trial were shared at the 2025 European Hematology Association (EHA) Congress.³ The safety population comprised 61 patients with heavily pretreated relapsed/refractory non-Hodgkin Lymphoma, including 13 patients with MCL.

The researchers reported that the rates of high-grade toxicities were low across the study population. Among all patients, CRS was reported in 26 (42.6%), including grade 1 in 13 patients (21.3%), grade 2 in 12 patients (19.7%), and grade 3 in 1 patient (1.6%). The median time to CRS onset was 7.0 days (range, 1-20), with a median CRS duration of 3.0 days (range, 1-17). Management of CRS included dexamethasone in 11 patients (18.0%) and tocilizumab in 15 patients (24.6%). Methylprednisolone and vasopressin were each used in 1 patient (1.6%).

Immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in 12 patients (19.7%), with grade 1 in 11 patients (18.0%) and grade 3 in 1 patient (1.6%). Median time to ICANS onset was 11.5 days (range, 2-30), and the median ICANS duration was 2.0 days (range, 1-47). ICANS management included dexamethasone in 6 patients (9.8%) and tocilizumab in 3 patients (4.9%). Grade ≥3 infections occurred in 3 patients (4.9%).

Galapagos NV also reported that its decentralized manufacturing platform enabled a rapid median vein-to-vein time of 7 days, which resulted in an attrition rate of 5%. Sixty-one (95%) of 64 enrolled patients received the treatment. Overall, 89% of patients were treated within 7 days post-leukapheresis, allowing them to avoid cytotoxic bridging therapy.

“By initiating lymphodepletion immediately after cell collection, we are able to infuse fresh product as soon as it becomes available, reducing patient attrition and potentially expanding access to CAR-T therapy. We observed a low 5% attrition rate, compared to rates of up to 30% reported in some clinical trials and real-world settings, and observed a manageable safety profile. These promising results suggest that rapid delivery of fresh, stem-like early memory cell therapies may offer meaningful clinical benefits for patients with R/R NHL,” said Fasan stated in a press release announcing the EHA data.³

“Decentralized cell therapy manufacturing is changing how we think about CAR-T eligibility. By enabling shorter vein-to-vein times and the use of fresh, early memory phenotype cells, this approach may allow for the inclusion of patients who would otherwise not be able to receive CAR-T therapy due to historically long manufacturing timelines,” Pim Mutsaers, MD, associate professor, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands, added in the news release.³

REFERENCES:

1. Galapagos NV. Galapagos NV announces U.S. FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted to GLPG5101 for the treatment of relapsed/refractory mantle cell lymphoma. Published February 10, 2025. Accessed August 12, 2025. https://tinyurl.com/vkvnfvps

2. Kersten MJ, Saevels K, Willems E, et al. Atalanta-1: A phase 1/2 trial of GLPG5101, a fresh, stem-like, early memory CD19 CAR T-cell therapy with a 7-day vein-to-vein time, for the treatment of relapsed/refractory non-Hodgkin lymphoma. Blood. 2024;144(Suppl 1):93. doi:10.1182/blood-2024-205360

3. Galapagos NV. Galapagos to present new ATALANTA-1 CAR-T data at EHA 2025 highlighting low toxicity and rapid decentralized delivery of fresh early memory enriched GLPG5101 in R/R NHL. Published June 12, 2025. Accessed August 12, 2025. https://tinyurl.com/3w4anmyy