Galapagos’ HESPERIA Study Tracks Long-Term Follow-Up for Patients Treated With the Company’s CAR-T Therapies
CGTLive® took a closer look at the phase 3 study, which is tracking patients for up to 15 years after their treatment with GLPG CAR-T products.
Galapagos NV is currently tracking the long-term follow-up of patients treated with the company’s various Galapagos (GLPG) chimeric antigen receptor T-cell (CAR-T) therapy products for hematologic malignancies in its phase 3 HESPERIA long-term follow-up study (NCT06652633).1
The study is assessing the long-term safety and efficacy of patients treated with GLPG CAR-T products over a period of 15 years posttreatment. According to the company’s pipeline page on its own website, GLPG CAR-T products include GLPG5101, which is being evaluated in the phase 1/2 ATALANTA-1 clinical trial (NCT06561425); GLPG5201, which is being evaluated in the phase 1/2 EUPLAGIA-1 clinical trial (CTIS: 2022-501686-47-00); and GLPG5301 which is being evaluated in the phase 1/2 PAPILIO-1 clinical trial (EU CT 2022-500782-27-00). GLPG5101 and GLPG5201 target CD19, and GLPG5301 targets BCMA. GLPG5101 is being evaluated for a wide range of relapsed/refractory (r/r) indications, including follicular lymphoma (FL), marginal zone lymphoma (MZL), primary central nervous system lymphoma (PCNSL), diffuse large B-cell lymphoma (DLBCL), DLBCL–Richter transformation (RT), high risk DLBCL, Burkitt lymphoma (BL), and chronic lymphocytic leukemia (CLL). On the other hand, GLPG5301 is being evaluated only for r/r multiple myeloma. GLPG5201 is being evaluated for r/r CLL and RT, although Galapagos notes that this product is being deprioritized in light of GLPG5101 potentially moving forward in CLL and RT indications.
“In line with our goal of becoming a more focused and streamlined organization, we are optimizing our CD19 CAR-T portfolio by prioritizing resources where they can have the greatest impact,” Paul Stoffels, MD, the chief executive officer and chairman of the board of directors at Galapagos, said in a February 2025 statement.2 “We are expanding the development of GLPG5101, our most advanced asset by extending its reach into additional aggressive B-cell malignancies, including RT of CLL, and are taking action to expand into double-refractory CLL. We are deprioritizing activities related to GLPG5201, our second CD19 CAR-T candidate, pending the advancement of GLPG5101 in those additional indications. At the same time, we are advancing the phase 1/2 study of GLPG5301 in multiple myeloma while strengthening our early-stage pipeline of next-generation, multi-targeting, armored cell therapies for hematological and solid tumors, accelerating innovation and driving long-term value creation. Additionally, through our partnership with Adaptimmune, we are progressing uza-cel, a T-cell receptor (TCR)-T-cell candidate for head and neck cancer, reinforcing our commitment to delivering transformational therapies.”
HESPERIA was initiated on September 9, 2024, and has an estimated completion date of July 2039.The study is expected to enroll approximately 546 patients in total. According to the clinicaltrials.gov page for HESPERIA, which was most recently updated on October 22, 2024, the study is currently recruiting at sites in Edegem and Liège, Belgium, Amsterdam and Leiden, the Netherlands, and Barcelona, Spain.
(Click to enlarge)
The primary end points for HESPERIA include the percentage of participants with targeted adverse events (AEs); detectable CAR transgene levels in peripheral blood; serious AEs considered related to the GLPG CAR-T therapy they received; at least 1% of T-cells in the blood sample or positive new malignancies; detectable replication-competent lentivirus in peripheral blood; and the percentage of patients who died with causes. The study’s secondary end points include the percentage of participants with disease progression, the time to patients’ next anticancer therapy, and overall survival. All of these end points will be measured for the time from infusion up to 15 years posttreatment.
HESPERIA is a single-arm study, and is open to all adult patients who received a GLPG CAR-T product in any clinical trial or Managed Access Program. As such, there are no specific exclusion or inclusion criteria for the study beyond those extant for the trial or program in which patients originally received the relevant CAR-T product. According to the clinicaltrials.gov page for ATALANTA-1, that study is open to patients with histologically confirmed r/r aggressive DLBCL;FL of grade 1, 2, or 3A; MZL; MCL; BL; or PCNSL. Participants must have disease that is measurable on the Lugano classification or via IPCG criteria for PCNSL; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; and adequate bone marrow,renal, hepatic, and pulmonary function. Patients with an ECOG performance status of 2 must additionally have a serum albumin of at least 3.4 grams per deciliter. On the other hand, ATALANTA-1 excludes patients with RT; those who have received certain prior treatments that are specified by the study protocol; those with another primary malignancy that requires more than surveillance or that has not been in remission for at least 3 years, with some exceptions in the protocol; those with active CNS involvement of their disease with neurological changes, with some exceptions in the protocol; and those with HIV, active hepatitis B, or active hepatitis C.
ATALANTA-1's investigational new drug (IND) application was cleared by the FDA in August 2024.3 Although, the trial had already been ongoing in Europe at the time, having been initiated on March 9, 2022. 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,” Stoffels said in an August 2024 statement.3 “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.”
REFERENCES
1. Our pipeline. Galapagos NV. Website. February 13, 2025. Accessed February 17, 2025. https://www.glpg.com/innovation/pipeline/
2. Galapagos Reports full year 2024 results and provides fourth quarter business update. News release. Galapagos NV. February 12, 2025. Accessed February 17, 2025. https://www.glpg.com/press-releases/galapagos-reports-full-year-2024-results-and-provides-fourth-quarter-business-update/
3. 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/
Keys to a Successful Cell and Gene Therapy Launch
February 16th 2025The success of cell and gene therapies relies not just on approvability but on affordability and accessibility. Innovative manufacturing, automation, and digital tools are key to expanding patient access and ensuring commercial viability.
