FDA Grants RMAT Designation to Novel CAR T-Cell Therapy for R/R Mantle Cell Lymphoma

The FDA granted regenerative medicine advanced therapy (RMAT) designation to the second-generation, anti-CD19/4-1BB CAR T-cell therapy GLPG5101 for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).¹

GLPG5101 is currently being evaluated in patients with relapsed/refractory B-cell non-Hodkin lymphomas, including MCL, in the phase 1/2 ATALANTA-1 trial (NCT06561425).

In a news release, Galapagos NV—the developer of GLPG5101—announced that as of a January 21, 2025, data cutoff, high objective response rates (ORRs) and complete response (CR) rates have been reported with the CAR T-cell therapy. The agent has displayed a manageable safety profile and low dropout rates. Additionally, low rates of high-grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) have been observed.

Prior data presented at the 2024 ASH Annual Meeting showed that among efficacy-evaluable patients with MCL (n = 8), the ORR and CR rate were both 100%.² in the population of patients with marginal zone lymphoma (MZL) or follicular lymphoma (n = 21), the ORR and CR rate were both 95%. Patients with diffuse large B-cell lymphoma (DLBCL; n = 13) achieved an ORR of 69% and a CR rate of 54%.

“This [RMAT] 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 NV, stated in a news release.¹ “With RMAT status allowing for closer collaboration with the FDA, this will enable additional opportunities for accelerated development and assessment timelines.”

What Is the ATLANTA-1 Trial Evaluating?

The phase 1/2 multicenter trial is evaluating the feasibility, safety, and efficacy of GLPG5101 in patients at least in patients at least 18 years of age with histologically confirmed relapsed/refractory DLBCL, grade 1, 2 or 3A follicular lymphoma, MZL, MCL, Burkitt lymphoma, primary central nervous system lymphoma (PCNSL), DLBCL with Richter transformation, or high grade B-cell lymphoma.³ Patients are required to have at least 1 measurable lesion per Lugano classification, with the exception of patients with primary central nervous system lymphoma (PCNSL) who are ineligible for autologous stem cell transplant after induction therapy; an ECOG performance status of 0 to 2; adequate bone marrow function; and adequate renal, hepatic and pulmonary function. Notably, patients with an ECOG performance status of 2 need to have a serum albumin level of at least 3.4 g/dL.

Key exclusion criteria comprise a history of another primary malignancy requiring intervention or that has not been in remission for at least 3 years; unresolved toxicity from prior anticancer therapy that has not resolved to baseline levels or to grade 2 or lower; active central nervous system (CNS) involvement; clinically significant cardiac disease; -primary immunodeficiency; or stroke or seizure within 6 months of screening.

In the phase 1 dose-escalation portion of the study, patients received GLPG5101 at dose levels of 50 × 10⁶, 110 × 10⁶ (DL2), or 250 × 10⁶ CAR-positive T cells, administered as a single infusion given on day 0.^1,3 The primary end points of phase 1 is safety—including the incidence of dose-limiting toxicities—and to determine the recommended dose for the Phase 2 part of the study.^1,3

In phase 2, investigators will evaluation GLPG5101 at the recommended phase 2 dose in malignancy-specific cohorts; those with MCL are being enrolled to cohort 4.³ ORR is the primary end point for all dose-expansion cohorts, with the exception of cohort 6b, where the primary objective is progression-free survival for patients with PCNSL receiving the agent as first-line consolidation.

References

1. Galapagos NV announces U.S. FDA regenerative medicine advanced therapy (RMAT) designation granted to GLPG5101 for the treatment of relapsed/refractory mantle cell lymphoma. News release. Galapagos NV. August 6, 2025. Accessed August 8, 2025. https://www.glpg.com/press-releases/galapagos-nv-announces-u-s-fda-regenerative-medicine-advanced-therapy-rmat-designation-granted-to-glpg5101-for-the-treatment-of-relapsed-refractory-mantle-cell-lymphoma/
2. Galapagos announces encouraging new results from ongoing phase 1/2 study of CD19 CAR T-cell therapy, GLPG5101, in patients with relapsed/refractory non-Hodgkin lymphoma. https://www.glpg.com/press-releases/galapagos-announces-encouraging-new-results-from-ongoing-phase-1-2-study-of-cd19-car-t-cell-therapy-glpg5101-in-patients-with-relapsed-refractory-non-hodgkin-lymphoma/
3. A study evaluating the safety and efficacy of GLPG5101 (19CP02) in participants with non-Hodgkin lymphoma (Atalanta-1). ClinicalTrials.gov. Updated May 5, 2025. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT06561425