Atalanta-1: A Phase 1/2 Trial of GLPG5101, a Fresh, Stem-like, Early Memory CD19 CAR T-Cell Therapy with a 7-Day Vein-to-Vein Time, for the Treatment of Relapsed/Refractory Non-Hodgkin Lymphoma

Background: CD19-targeted CAR T-cell therapies offer the potential for durable remission in patients (pts) with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL), who typically have poor prognoses. Shorter vein-to-vein time, robust in vivo expansion, and preservation of early T-cell phenotypes during manufacturing may improve safety and efficacy in pts with NHL. GLPG5101 is a fresh, stem-like, early memory phenotype CD19 CAR T-cell therapy manufactured using a rapid decentralized platform enabling a 7-day vein-to-vein time. Here, we present updated results from the ongoing ATALANTA-1 study of GLPG5101 for R/R NHL.

Methods: ATALANTA-1 (CTIS: 2022-502661-23-00) is a Phase (Ph)1/2 study of GLPG5101 in pts with R/R diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Burkitt lymphoma, or primary central nervous system lymphoma. Primary objectives are safety, establishment of a recommended Ph2 dose in Ph1, and efficacy (objective response rate [ORR]) in Ph2. Secondary objectives encompass manufacturing feasibility, safety, efficacy (including duration of response and minimal residual disease [MRD]), and pharmacokinetics. The expansion and persistence of GLPG5101 were quantified in peripheral blood using PCR. MRD in plasma was evaluated using the clonoSEQ assay.

Results: As of April 25, 2024, 53 pts had undergone leukapheresis: 49 had received an infusion, with 47 (96%) receiving a fresh product. A 7-day vein-to-vein time was achieved in 43/47 (91%) pts. In Ph1, 2 pts received less than the prespecified minimum dose and were not included in the analyses. Data for 45 pts receiving a fresh infusion were analyzed (R/R DLBCL n=13 [all Ph1]; MCL n=8; FL n=19; MZL n=5). Median (range) age was 66.5 (25–78) years in Ph1 and 67.0 (40–81) years in Ph2. Median (range) number of prior therapies was 2.5 (1–7) in Ph1 and 3.0 (2–11) in Ph2.

Most Grade ≥3 treatment-emergent adverse events (reported up to 14 weeks post-infusion) were hematological. CRS was reported in 9/20 (45%) Ph1 pts (Grade ≤2 n=8; Grade 3 n=1) and 10/25 (40%) Ph2 pts (all Grade ≤2). ICANS was reported in 6/20 (30%) Ph1 pts (all Grade 1) and 4/25 (16%) Ph2 pts (Grade 1 n=3; Grade 3 n=1). Of all 49 pts who received an infusion, 2 died during the treatment period and 1 died during follow-up.

Three pts had not reached first response assessment at data cutoff and were excluded from the efficacy analyses. Median (range) follow-up in the study was 13.0 (0–24) months in Ph1 and 5.4 (1–14) months in Ph2. Across Ph1 and Ph2, 37/42 efficacy-evaluable pts responded to treatment (ORR 88%), with 35/42 achieving complete response (CR; CR rate [CRR] 83%). All pts with MCL (8/8) achieved CR (ORR and CRR 100%); 20/21 pts with FL/MZL responded (ORR and CRR 95%); 9/13 pts with DLBCL responded (ORR 69%) with 7 achieving CR (CRR 54%). Of pts with DLBCL who received the higher dose, 6/7 responded (ORR 86%) with 5 achieving CR (CRR 71%).

At data cutoff, of 11/16 (69%) Ph1 pts who responded to treatment, 10 had an ongoing response and 1 had completed the study while in CR. After an initial response, 3 pts with DLBCL and 1 with MCL progressed. In Ph2, 21/21 (100%) of responding pts had an ongoing response. MRD negativity occurred in 12/15 (80%) evaluable pts who achieved CR (DLBCL n=1; MCL n=2; MZL n=2; FL n=7). All MRD-negative pts with a minimum follow-up of 6 months (n=11) were in ongoing CR at data cutoff.

The proportion of early T-cell phenotypes (naïve/stem cell memory and central memory) of CD4⁺ and CD8⁺ CAR T cells was significantly increased in the final product (FP) compared with the starting material (SM). A median increase in the CD4:CD8 ratio of CAR⁺ T cells in the FP was observed compared with the SM. GLPG5101 demonstrated robust in vivo expansion across all dose levels and indications, and persisting CAR T cells were detected in peripheral blood up to 21 months post-infusion.

Conclusions: Results from the ongoing ATALANTA-1 study show a manageable overall safety profile, with low rates of Grade ≥3 CRS and ICANS and high antitumor activity in all NHL subtypes studied. GLPG5101, a fresh, stem-like, early memory CD19 CAR T-cell therapy manufactured using a rapid decentralized platform, showed robust in vivo expansion and durable persistence. Treatment with GLPG5101 led to promising efficacy and safety across indications in heavily pretreated pts with R/R NHL.