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
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.