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Publications

Journal Article Ahead of print

PubMed: 41101155 DOI: 10.1016/j.esmoop.2025.105844

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.

ESMO Open 10(11):105844

Authors: J Vansteenkiste, I Demedts, K Cuppens, E Pons-Tostivint, E Wauters, F J Borm, A Sibille, B Colinet, M Pérol, W S M E Theelen, B Biesma, C Van De Kerkhove, E Buchmeier, F C Althoff, S Derijcke, D Moro-Sibilot, K Laulagnier, E Halioua, L Levy, M Genin, S Michel, C Dedry, C Duchayne, M Collodoro, F Renard, S Adriaenssens, B De Vos, F Cantero, J Plumas, M Skrzypski

Affiliations

  • Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven, Leuven, Belgium.
  • Pulmonary Diseases, AZ Delta Campus Rumbeke, Roeselare, Belgium.
  • Pulmonology & Thoracic Oncology Department, Jessa Hospital, Hasselt, Belgium.
  • Medical Oncology Department, Nantes University Hospital, Nantes, France.
  • Respiratory Oncology Unit (Pulmonology), University Hospitals Leuven, Leuven, Belgium.
  • Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
  • Department of Pulmonology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
  • Pneumology Department, GHdC, Grand Hôpital de Charleroi, Site Notre Dame, Charleroi, Belgium.
  • Medical Oncology Department, Centre Léon Bérard, Lyon, France.
  • Thoracic Oncology Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Pulmonology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
  • Clinical Study Centre, Vitaz campus Sint-Niklaas Moerland, Sint-Niklaas, Belgium.
  • Hematology & Oncology Department, Kliniken der Stadt Koln gGmbH, Köln, Germany.
  • Hemato-Oncology Department, Universitätsklinikum Frankfurt (Johannes-Wolfgang Goethe-Universität), Frankfurt Am Main, Germany.
  • Pulmonology - Thoracic Oncology, AZ Groeninge, Campus Kennedylaan, Kortrijk, Belgium.
  • Thoracic Oncology, SHUPP, CHU Grenoble-Alpes, Grenoble, France.
  • PDC(∗)line Pharma France, Grenoble, France.
  • PDC(∗)line Pharma Belgique, Liège, Belgium.
  • RLM Consulting, Louvain-la-Neuve, Belgium.
  • Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.

Abstract

BACKGROUND

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.

PATIENTS AND METHODS

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).

RESULTS

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).

CONCLUSIONS

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.

MeSH

Cells, Lung, Safety, Vaccines, Neoplasms, Carcinoma, Non-Small-Cell Lung, Immune Checkpoint Inhibitors, Lung Neoplasms, Small Cell Lung Carcinoma, Immunity, Therapeutics, Cancer Vaccines