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 (Charles, 2020; Lenogue 2021). Stage II/IIIA (cohort A) or stage IV, PD-L1≥50% (cohort B; +pembrolizumab) non-small cell lung cancer (NSCLC) patients received weekly intravenous and subcutaneous IMP for 6 times at two dose levels. Early safety and clinical activity findings with IMP were presented at ESMO Paris 2022. We report here the analysis of immune response of the first 3 cohorts of patients.
Several circulating immune parameters were monitored at different times before and after vaccination (W1, W4, W10) using specific assays developed by the sponsor: leukocyte count and determination of peptide-specific CD8+ T cells, for which a limit of quantification (LOQ) was defined to better assess the fold changes of the cell expansion. In addition, tumor microenvironment (TME) was analyzed by multifluorescent immunochemistry.
23 of the 25 patients included received at least 4 doses and were evaluable. No major changes in circulating lymphocyte frequencies (B cells, NK cells, CD4+, CD8+, or Treg T cells) were observed during treatment. In addition, no major cell activation (CD25+, CD54, or DR+) was noted. In contrast, PDC*lung01 induced peptide-specific CD8+ T cell expansion in all 3 cohorts at different levels. An immune response was induced against lung antigens in 33%, 45% and 67% in A1, A2 and B1 cohort, respectively. The intensity of the immune response was proportional to the IMP dose and to the combination with pembrolizumab. When possible, CD8+ T cells were sorted for TCR repertoire analysis, illustrating the modelling and dynamics of the immune response. Detailed findings will be graphically presented at the meeting.
Treatment with PDC*lung01 induces an anti-tumour immune response in a significant number of patients which appears to be enhanced by the combination with pembrolizumab.
NCT03970746.
PDC*line Pharma SAS.
PDC*line Pharma SAS.
A. Sibille: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dome, AstraZeneca, Bristol Myers Squibb, Roche, Pfizer. J. Plumas: Financial Interests, Personal, Full or part-time Employment: CSO of PDC*line Pharma; Financial Interests, Personal, Stocks/Shares: PDC*line Pharma. I. Demedts: Financial Interests, Personal, Other, invited speaker and participation in Advisory Board meetings: AstraZeneca, BMS, Boehringer, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. E. Pons-Tostivint: Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Daiichi Sankyo, Sanofi, PDC line, Takeda. M. Collodoro: Financial Interests, Personal, Full or part-time Employment: PDC*line; Financial Interests, Personal, Stocks/Shares: PDC*line. K. Al Badawy: Financial Interests, Personal, Full or part-time Employment: QC Department, PDC*line Pharma SA. C. Duchayne: Financial Interests, Personal, Full or part-time Employment: QC Department, PDC*line Pharma SA. C. Debruyne: Financial Interests, Institutional, Other, Consultant as Medical Director: PDC*line Pharma SAS; Financial Interests, Institutional, Stocks/Shares: PDC*line Pharma SAS. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim. E.L. Buchmeier: Financial Interests, Personal, Invited Speaker, and congress sponsoring: Takeda; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Invited Speaker: BMS, AstraZeneca, Novartis, MSD, Janssen Cilag, PDC Line Pharma, Roche, GSK, Novartis; Non-Financial Interests, Personal, Member: Political Party FDP. K. Cuppens: Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche, AstraZeneca, Merck Sharp Dohme, Bristol Myers Squibb, Boehringer Ingelheim, Bayer; Financial Interests, Personal, Invited Speaker: Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, F. Hoffmann-La Roche; Financial Interests, Personal, Expert Testimony: Merck Sharp & Dohme, AstraZeneca. J.F. Vansteenkiste: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, MSD, Pfizer, Roche, Janssen, Merck, Novartis, PDC*line, Sanofi; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Novartis, Janssen, Eli Lilly, Roche; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.