119MO - Phase I/II trial evaluating the innovative therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with untreated stage IV non-small cell lung cancer

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-L1≥50% 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. Table: 119MO

B2 cohort: Efficacy parameters

Clinical trial identification

NCT03970746.

Legal entity responsible for the study

PDC*line Pharma SAS.

Funding

PDC*line Pharma SAS.

Disclosure

J.F. Vansteenkiste: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, Janssen, MSD, Merck, PDCline, Pfizer, Roche, Sanofi, Boehringer-Ingelheim, Transgene; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, MSD, Sanofi, Merck. K. Cuppens: Financial Interests, Personal, Advisory Board: Hoffmann-La Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, Merck Sharp & Dohme, AstraZeneca, Bristol Myers Squibb, Pierre Fabre Oncology, Amgen, Daiichi Sankyo, Janssen, Iteos Therapeutics; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Sharp & Dohme, F. Hoffmann-La Roche, Janssen, Merck Sharp & Dohme. I. Demedts: Financial Interests, Personal, Other, invited speaker and participation in advisory board meetings: AstraZeneca, BMS, Boehringer, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. M. Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, Ipsen, Novocure, AbbVie, Anheart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Symposium: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Advisory Board, Expert Testimony: AstraZeneca; Financial Interests, Personal, Steering Committee Member, Steering Committee Member: Lilly; Financial Interests, Institutional, Local PI, Local PI: AbbVie, Amgen, Anheart Therapeutics, Apollomics, Arrivent Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Innate Pharma, Roche; Financial Interests, Institutional, Research Grant, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Trial Chair, Trial Chair: Anheart Therapeutics; Financial Interests, Personal, Steering Committee Member, Idmc Chair: PharmaMar, Sophiagenetics; Financial Interests, Personal, Steering Committee Member, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. W. Theelen: Financial Interests, Institutional, Research Grant, From AstraZeneca, MSD and Sanofi/Regeron for investigator-initiated studies; Netherlands Cancer Institute. E. Wauters: Financial Interests, Institutional, Other, Consulting fee: MSD, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Roche, Medimix; Financial Interests, Institutional, Writing Engagement, Payment for manuscript writing: BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, MSD. B. Colinet: Financial Interests, Personal, Advisory Board: MSD, Roche; Financial Interests, Personal, Invited Speaker: Chiesi, BMS; Non-Financial Interests, Personal, Member of Board of Directors: AFBOT. E.L. Buchmeier: Financial Interests, Personal, Advisory Board: Ipsen, BMS, Janssen Oncology, AstraZeneca; Financial Interests, Personal, Invited Speaker, and congress sponsoring: Takeda; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, Novartis, MSD, Janssen Cilag, PDC Line Pharma, Roche, GSK, Novartis. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi, Roche, Daichi Sankyo; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Daiichi Sankyo, Sanofi, PDC Line, Takeda, Amgen. A. Sibille: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, AstraZeneca, Bristol Myers Squibb, Roche, Pfizer. J. Plumas: Financial Interests, Personal, Full or part-time Employment, I am CSO of PDC*line Pharma: PDC*line Pharma; Financial Interests, Personal, Stocks/Shares: PDC*line Pharma. S. Adriaenssens: Financial Interests, Institutional, Full or part-time Employment: PDC*line Pharma. F. Cantero: Financial Interests, Personal, Full or part-time Employment, Medical Director: PDC*line Pharma; Financial Interests, Personal, Stocks/Shares: PDC*Line Pharma SA. All other authors have declared no conflicts of interest.