Innovative therapeutic cancer vaccine PDC∗lung01 with or without anti-PD-1: an open-label, dose-escalation phase I/II study in non-small-cell lung cancer

While immune checkpoint inhibitors have revolutionized the treatment of non-small-cell lung cancer (NSCLC), many patients still suffer from either primary or acquired treatment resistance. Stimulation of antitumor cellular immunity with a therapeutic cancer vaccine in combination with anti-programmed cell death (ligand) protein 1 [PD-(L)1] may improve outcome. PDC ∗ lung01 is a cancer vaccine made of irradiated plasmacytoid dendritic cells loaded with six NSCLC tumor antigens (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, and Survivin), and available as a ready-to-use product. This open-label, dose-escalation, multicenter, phase I/II study assessed the safety profile, clinical activity, and immunogenicity of PDC ∗ lung01 at low or high doses, either as a single agent in resected NSCLC (cohorts A) or with anti-PD-1 in metastatic NSCLC with PD-L1 ≥ 50% (cohorts B). The primary objective was vaccine-related dose-limiting toxicities (DLTs). Secondary objectives included safety profile, T-cell response against vaccine antigens in all cohorts, and clinical activity in cohort B2 (high-dose PDC∗lung01 with anti-PD-1): objective response rate (ORR) and 9-month progression-free survival (9mPFS). Median follow-up was 20 months [95% confidence interval (CI) 14-26 months] in all enrolled patients ( N = 73). Most adverse events were mild to moderate; only one patient (2%) in cohort B2 reported a related DLT. In the combination of PDC∗lung01 (high-dose) with anti-PD-1 ( N = 45), the confirmed ORR was 51% (80% CI 41% to 62%), the 9mPFS estimate was 47% (80% CI 37% to 57%), and the median PFS was 9 months (95% CI 5.0-24 months). PDC ∗ lung01 elicited tumor antigen-specific T-cell expansions in 50%-67% of patients and PFS duration correlated positively with immune response intensity ( P = 0.04). PDC ∗ lung01 was immunogenic and had a manageable safety profile in all cohorts and met the predefined clinical objectives when combined with anti-PD-1 in metastatic NSCLC. Median PFS was positively correlated with antigen-specific T-cell expansions. • A novel allogeneic plasmacytoid dendritic cell-based vaccine was tested alone or with anti-PD-1. • For the first time we present efficacy data in combination with first-line pembrolizumab for untreated metastatic NSCLC. • The vaccine was well tolerated in both monotherapy and combination settings. • Confirmed ORR was 51% (80% CI 41% to 62%); median PFS was 9 months (95% CI 5.0-23.6 months). • Most patients showed an immune response, which correlated significantly with PFS duration.