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

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 2^nd 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 1^st cohort (n=3, 50x10^6 19CP02 cells) has been completed with no dose limiting toxicities (DLT). The 2^nd 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 1^st 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.