Abstract CT021: Preliminary clinical results of a therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with stage IV NSCLC
Authors: Theelen Willemijn , Perol Maurice , Cuppens Kristof , Demedts Ingel , Borm Frank , Biesma Bonne , Wauters Els , Colinet Benoit , Buchmeier Eva-Lotte , Althoff Friederike , Pons-Tostivint Elvire , Van de Kerkhove Charlotte , Moro-Sibilot Denis , Sibille Anne , Derijcke Sofie , Skrzypski Marcin , Plumas Joel , De Vos Beatrice , Debruyne Channa , Cantero Frederique , Adriaenssens Stefanie , Renard Florence , Vansteenkiste Johan 
Published: April 2024

Abstract
Background PDC*lung01 (IMP) is a therapeutic cancer vaccine 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 peptide-specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-PD-1.
Methods In this phase I/II study, HLA-A*02 positive NSCLC pts were enrolled in 4 cohorts: resected stage II/IIIA in adjuvant setting treated with low dose (A1) or high dose (A2) of IMP following SOC; or untreated stage IV NSCLC with measurable disease, PD-L1≥50% and no targetable driver mutation, treated with low dose (B1) or high dose (B2) of IMP in combination to pembrolizumab 200mg q3w, continuously. IMP was simultaneously administered by SC and IV route weekly for 6 consecutive doses. Objective response rate (ORR) and progression-free survival (PFS) were assessed in cohort B2. We report herein preliminary efficacy results of the first 21 pts analysed when the 19th evaluable patient reached the 9-months PFS and the safety of 38 pts.
Results Out of 21, 19 pts receiving at least 5 doses of IMP and having 1 post-baseline radiological evaluation were evaluated. The median follow-up was 12.5 months. The best objective response (BOR) included 12 PR (63.2%) and 7 SD (36.8%) with ORR of 63.2% (80% CI 45.9% - 78.2%) and a disease control rate (DCR) of 94.7%. The 9mPFS according to the Kaplan-Meier estimate was 52.1% (80% CI 36.5% - 65.56%). The mPFS was 10.9 months. The median duration of response was 9.49 months. An antigen-specific CD8+ T-cell response was induced against the lung antigens of the IMP in 68.4% of pts. Immune responses with remarkable expanded anti-tumor CD8+ T-cells were observed both in PR and SD. More immune response results will be available in the final analysis of the 45 pts of cohort B2. Treatment-related AEs (TRAEs) were mostly Grade 1-2. Only 1 severe TRAE occurred, a Grade 4 allergic infusion-related reaction, leading to IMP discontinuation. Thirteen pts experienced a serious AE, of which 3 were considered causally related to the IMP.
Conclusions The BOR, ORR, DCR, PFS, duration of response and safety of PDC*lung01 in combination with anti-PD-1 showed encouraging signals suggesting that this combination may provide a clinical meaningful tumour response in stage IV NSCLC population with a mild safety profile. Interestingly, the immune response observed confirms the mechanism of action of the IMP in relation to clinical activity.
Citation Format: Willemijn Theelen, Maurice Perol, Kristof Cuppens, Ingel Demedts, Frank Borm, Bonne Biesma, Els Wauters, Benoit Colinet, Eva-Lotte Buchmeier, Friederike Althoff, Elvire Pons-Tostivint, Charlotte Van de Kerkhove, Denis Moro-Sibilot, Anne Sibille, Sofie Derijcke, Marcin Skrzypski, Joel Plumas, Beatrice De Vos, Channa Debruyne, Frederique Cantero, Stefanie Adriaenssens, Florence Renard, Johan Vansteenkiste. Preliminary clinical results of a therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with stage IV NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT021.