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4637 Initial Clinical Results of Atalanta-1, a Phase I/II Trial of Point-of-Care Manufactured GLPG5101 (19CP02) in RR NHL

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Sébastien Anguille1*, Ilse Kuipers2*, Kirsten Saevels, MD3, Yves Beguin, MD, PhD4, Anna Van Muyden, MSc5*, Christian Jacques, MD5 and Marie Jose Kersten, MD, PhD2

1Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium
2Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, Netherlands
3Division of Hematology, Antwerp University Hospital, Antwerp, Belgium
4Department of Hematology, CHU Liege, University of Liege, Liege, Belgium
5CellPoint, a Galapagos company, Leiden, Netherlands

Background: CD19-directed chimeric antigen receptor T cell (CAR-T) therapy has dramatically improved survival for patients with relapsed/refractory (RR) Non-Hodgkin Lymphoma (NHL). CellPoint has developed a decentralized, point‑of-care manufacturing solution with the Lonza’s Cocoon™ platform which enables clinicians to administer autologous CD19 CAR-T treatments within 7 days of apheresis, without complex logistics or cryopreservation, with the aim of improving product attributes while significantly decreasing the vein-to-vein time. This has the potential to overcome major limitations of currently available CAR-T therapies, such as capacity issues resulting in high costs, limited manufacturing slots, waiting lists, and long vein-to-vein times.

Methods: Atalanta-1/CP0201-NHL (EudraCT 2021-003272-13) is a Phase I/II, multicenter study in which we evaluate the feasibility, safety, and efficacy of point-of-care manufactured GLPG5101 (19CP02) in patients with RR B-cell NHL. GLPG5101 is a 2nd generation anti-CD19/4-1BB CAR-T product, administered as a fresh product in a single fixed dose. Patients with RR Diffuse Large B-Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL) or Mantle Cell Lymphoma (MCL) are eligible. Three dose levels are planned: 50x10^6, 110x10^6 and 250x10^6 CAR+ viable T cells. The Phase I/II is using a Bayesian Optimal Interval (BOIN) design with an expected sample size of 15 patients for Phase I. The primary endpoints of Phase I are safety and establishing a recommended dose for Phase II (RP2D). Following screening and enrollment, patients undergo leukapheresis of mononuclear cells. During manufacturing of GLPG5101 (19CP02), patients receive Cyclophosphamide (300 mg/m2/day) and Fludarabine (30 mg/m2/day) for 3 days as conditioning chemotherapy. After a resting period of at least 2 days, GLPG5101 (19CP02) is administered via intravenous infusion. Patients are hospitalized for at least 7 days and the end-of-study visit is at 14 weeks post CAR-T treatment.

Results: Six patients have been enrolled in the ongoing Phase I part of the study. The median age is 67 years (58-77 yrs), 4/6 patients are male. Enrolled patients were diagnosed with RR MCL (n=3), RR DLBCL (n=2) and RR FL (n=1) - table 1. Five patients were infused within 7 days of leukapheresis, 1 is pending leukapheresis. The 1st cohort (n=3, 50x10^6 19CP02 cells) has been completed with no dose limiting toxicities (DLT). The 2nd cohort (n=3, 110 x10^6 19CP02 cells) is ongoing with no DLT observed at time of writing. Most adverse events are grade 1-2 and mostly hematological - table 2. Pleural effusion worsened to grade 4 before complete disappearance occurred at Day 44. No grade 3-4 Cytokine Release Syndrome or neurotoxicity has been observed thus far. Efficacy data in the first cohort are available at 28 days post CAR-T infusion; 2 patients with MCL had CR, 1 patient with DLBCL had Stable Disease. High peak expansion levels were observed ranging from 2.6x10^5 - 4.0x10^5 CAR-T copies/µg DNA in the 1st dose cohort.

Conclusion: GLPG5101 (19CP02) manufactured at the point-of-care, administered as a fresh product with a vein-to-vein time of only 7 days, is a new CAR-T therapeutic option with limited toxicity and promising efficacy. Safety and efficacy results of this ongoing phase 1 trial, including CAR T-cell expansion and persistence data will be updated at the time of this meeting.

The Atalanta-1/CP0201-NHL study is sponsored by CellPoint BV, a Galapagos company, with EU registration number 2021-003272-13.

Disclosures: Van Muyden: CellPoint, a Galapagos company: Current Employment. Jacques: CellPoint BV, a Galapagos company: Consultancy. Kersten: BMS/Celgene: Honoraria, Research Funding; Miltenyi Biotech: Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; Novartis: Honoraria; Adicet Bio: Honoraria; Takeda: Honoraria; Roche: Honoraria, Research Funding.

*signifies non-member of ASH