On June 12, 2023 Galapagos NV (Euronext & NASDAQ: GLPG) reported that it will feature the CAR-T point-of-care manufacturing platform and will present previously disclosed initial Phase 1/2 data with CD19 CAR-T candidate, GLPG5201, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 congress, taking place from 8 June to 11 June 2023 in Frankfurt, Germany (Press release, Galapagos, JUN 5, 2023, View Source [SID1234632656]).
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"Patients who develop rrCLL and become resistant to new agents have a very poor prognosis and a significant high unmet medical need for novel therapeutic options such as CAR-T cell therapy. The previously disclosed initial efficacy, safety and feasibility data from the ongoing EUPLAGIA-1 study with our CD19 CAR-T candidate, GLPG5201, manufactured at point-of-care, are encouraging, and we are on track to provide Phase 1 topline results around mid this year," said Jeevan Shetty, Head of Clinical Development Oncology at Galapagos. "Our innovative approach in CAR-T cell therapy development and manufacturing underscores our commitment to accelerating transformational innovation to address the unmet needs of patients with advanced cancers, and we very much look forward to meeting and connecting with you at our booth."
Details of the abstract P1399:
Title Authors Presentation date/time
Initial Clinical Results of Euplagia-1, a Phase I/II Trial of Point-of-Care
Manufactured GLPG5201 in R/R CLL/SLL with or without Richter’s transformation Nuria Martinez-Cibrian, Sergi Betriu, Valentin Ortiz-Maldonado, Daniel Estban, Leticia Alserawan, Mercedes Montoro, Anna DD van Muyden, Maike Spoon, Margot J. Pont, Christian Jacques, Julio Delgado Abstract
Poster presentation on
9 June 2023, 18:00 – 19:00 CET
At the safety and efficacy analysis cut-off date of 9 January 2023, 7 patients diagnosed with rrCLL (including 4 patients with RT) were enrolled in the EUPLAGIA-1 study (n=4 at dose level 1 (DL1); n=3 at dose level 2 (DL2)). All patients received GLPG5201 as a fresh infusion with a median vein-to-vein time of 7 days. The dose levels that are evaluated in the Phase 1 part of the study are 35×106 (DL1), 100×106 (DL2) and 300×106 (dose level 3 (DL3)) CAR+ viable T cells.
The initial results from these 7 patients that were eligible for efficacy analysis (cut-off date: 9 January 2023) indicated that a 7-day vein-to-vein time is feasible and demonstrated strong and consistent in vivo CAR-T expansion levels. Moreover, the initial efficacy results are encouraging with an objective response rate (ORR) of 100% observed. 6 out of 7 patients (86%) reached a complete response (CR) and all Richter’s patients achieved a CR. A duration of response of up to 7.9 months has been reported and follow-up is ongoing. Only 1 patient (DL1) progressed (progressive disease, (PD) after partial response (PR)) and had a CD19-negative relapse with confirmed RT.
In the safety analysis of these 7 patients, adverse events were consistent with the known toxicities of CD19 CAR-T treatment. None of the patients experienced a CRS higher than grade 2 at both dose levels and no ICANS was reported. No dose limiting toxicities (DLTs) were reported and the majority of grade ≥3 adverse events were hematological. Only one serious adverse event was reported at DL2 with a patient experiencing a CRS grade 2, but the event was resolved after 7 days. Patient recruitment of the study is ongoing.
About point-of-care manufacturing
CellPoint (a Galapagos company) has developed, in a strategic collaboration with Lonza, a novel point-of-care supply model, which is designed to enable clinicians to administer fresh CAR-T cells within 7 days of leukapheresis, without complex logistics or cryopreservation, thereby aiming to address important limitations of current CAR-T treatments. The proprietary platform consists of CellPoint’s end-to-end xCellit workflow management and monitoring software, and Lonza’s Cocoon Platform, a functionally closed, automated manufacturing platform for cell therapies. This novel point-of-care model is compliant with the EMA and FDA guidance for clinical trials.
About the EUPLAGIA-1 study (EudraCT 2021-003815-25)
EUPLAGIA-1 is an ongoing Phase 1/2 open-label, multi-center study evaluating the feasibility, safety, and efficacy of point-of-care manufactured GLPG5201 in patients with rrCLL and small cell lymphocytic lymphoma (rrSLL), with or without RT. GLPG5201 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as intravenous infusion of a fresh product candidate in a single fixed dose. Patients with CD19+ rrCLL or rrSLL with ≥2 lines of prior therapy are eligible to participate, and patients with RT are eligible regardless of prior therapy. The primary objective of the Phase 1 part of the study is to evaluate safety and determine the recommended dose for the Phase 2 part of the study. The primary objective of the Phase 2 part of the study is to assess the ORR and the secondary objectives include the analysis of the complete response rate (CRR), duration of response, progression free survival, overall survival, safety pharmacokinetic profile, and feasibility of point-of-care manufacturing.
The dose levels that are evaluated in the Phase 1 part of the study are 35×106 (DL1), 100×106 (DL2) and 300×106 (DL3) CAR+ viable T cells. The study uses a Bayesian Optimal Interval (BOIN) design (n=15 patients) for Phase 1. Following screening and enrolment, patients will receive ibrutinib daily until leukapheresis of mononuclear cells. During GLPG5201 manufacturing, patients receive cyclophosphamide (300 mg/m2/day)/fludarabine (30 mg/m2/day) for 3 days. After a resting period of at least 2 days, GLPG5201 is administered via intravenous infusion. All patients remain hospitalized for at least 7 days and the end-of-study visit is at Week 14 post CAR-T infusion. Phase 1 patient recruitment is ongoing to establish a recommended dose for Phase 2.
About chronic lymphocytic leukemia and small cell lymphocytic lymphoma
Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes, which are usually monoclonal in origin. CLL and small cell lymphocytic lymphoma (SLL) are essentially the same type of B-cell non-Hodgkin lymphoma (NHL), with the only difference the location where the primary cancer occurs. CLL affects B-cells in the blood and bone marrow and SLL cancer cells are located in lymph nodes and/or the spleen3. RT is an uncommon clinicopathological condition observed in patients with CLL. It is characterized by the sudden transformation of the CLL into a significantly more aggressive form of large cell lymphoma and occurs in approximately 2-10% of all CLL patients. CLL/SLL usually follows an indolent course and is an incurable disease. Patients who develop relapsed and refractory disease and become resistant to new agents have a dismal prognosis and a high unmet medical need for new therapeutic options such as CAR-T cells. With estimated incidence of 4.7 new cases per 100,000 individuals, CLL/SLL are the most prevalent lymphoid malignancies and are the most common adult leukemias in the US and in Europe.