120MO Inupadenant combined with chemotherapy in patients with non-squamous NSCLC progressing on or after immune checkpoint inhibitor therapy: Results from dose-finding part of the A2A-005 trial

Background: PDC*lung01 (IMP) is an innovative therapeutic cancer vaccine, synergistic with anti-PD-1, based on an irradiated plasmacytoid dendritic cell line loaded with HLA-A*02:01-restricted peptides (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A), able to prime and expand antigen-specific CD8+ T cells in vitro and in vivo.Methods: This phase I/II study (NCT03970746) enrolled HLA-A*02 positive NSCLC pts in 4 cohorts: 2 cohorts with IMP in resected stage II/IIIA in adjuvant setting following SoC (low A1 and high dose A2) and 2 cohorts with IMP plus pembrolizumab 200 mg q3w in untreated stage IV NSCLC with PD-L150% and no targetable driver mutation (low B1 and high-dose B2).IMP was administered by SC and IV routes weekly for 6 consecutive doses.We report cohort B2 efficacy results of the 42 evaluable pts from the designed per protocol population: objective response rate (ORR) and progression-free survival (PFS).Results: At this data cut-off, the last pt reached 9 months (mo) follow-up (FU) with a median FU of 19.5mo (95%CI 13.8-25.6).Confirmed ORR was 55% (80%CI 43.7%-65.4%)reaching the predefined target (15% increase compared to Keynote-042).The 9mPFS was 49% (80%CI 38.5%;58.3%),and mature median PFS reached 8.87mo (95% CI 4.3-23.6)(Table ).An antigen-specific CD8+ T-cell response was induced in 56% of pts.Remarkable expansions of anti-tumor CD8 +T-cells up to 2.3% of total CD8+T-cells were observed.Treatment-related AEs (TRAEs) were mostly grade 1-2 with one grade 4 allergic infusion-related reaction.Fourteen pts experienced a serious AE, 3 considered related to the IMP.Conclusions: This primary analysis shows that PDC*lung01 + pembrolizumab may provide a meaningful clinical activity compared to anti-PD1 alone, with a mild safety profile.PDC*lung01 is biologically active inducing strong immune response in a significant proportion of pts.Clinical trial identification: NCT03970746.