Abstract 21P
Background
Cancer vaccines may synergize with immune checkpoint inhibitors. PDC*lung01 (IMP) is based on an irradiated plasmacytoid dendritic cell line loaded with 7 HLA-A*02:01-restricted tumor peptides, able to prime and expand antigen-specific CD8+ T cells in vitro and in vivo.
Methods
73 HLA-A*02:01 positive pts were enrolled and received IMP either at low (cohort A1) or high dose (cohort A2) in adjuvant setting (resected stage II/IIIA), and either at low (cohort B1) or high dose (cohort B2) in combination with pembrolizumab 200 mg Q3W in untreated stage IV with PD-L1≥50%. IMP was administered by SC and IV routes Q1W × 6.
Results
At the cut-off date (18Jul2024), the median follow up was 20.1 months (mo) (95%CI 14.3–26.1). Within the safety population (n=73), treatment-related adverse events (AEs) were mostly grades 1–2 with only one grade 4 (anaphylactic reaction). 19 pts (26%) experienced a serious AE, 4 (5.5%) considered related to the IMP. The confirmed objective response rate (ORR) in cohort B2 (n=42) was 55%, reaching the predefined clinical study objective and in line with the preliminary results observed in cohort B1 in 6 pts (ORR: 67%). The median progression-free survival (PFS) in cohort B2was 8.87mo (Table). Overall survival of cohorts B is immature but 63% of pts are still alive at the cutoff date. Antigen-specific CD8+ T cell responses were observed in 50% and 64% of cases with vaccine alone (cohorts A1, A2), and in 67% and 56% in combination with pembrolizumab (cohorts B1, B2) with a dose effect and synergy with anti-PD-1 in the immune response intensity. There was a significant positive correlation between the intensity of the immune response and the PFS (mo) in cohort B2 (p=0.0396).
Table 21PEfficacy in B1 and B2 cohorts
| B1 cohort Per protocol population n=6 | B2 cohort Design Per protocol population n=42 | |
| Follow-up, median Confirmed ORR, n (%) | 26.3 | 19.5 |
| 95% CI [26.1-NR] | 95% CI [13.8–25.6] | |
| 4 (67) | 23 (55) | |
| 80% CI [33.3–90.7] | 80% CI [43.7–65.4] | |
| Duration of response, median, mo PFS, median, mo | Not reached | Not reached |
| 95% CI [12.2-NR] | 95% CI [7.7-NR] | |
| Not reached | 8.87 | |
| 95% CI [2.1-NR] | 95% CI [4.3–23.6] |
Conclusions
PDC*lung01 combined with pembrolizumab provides meaningful clinical activity, with a mild safety profile, and a confirmed correlation between the immune response intensity and the PFS.
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, Boehringer-Ingelheim, Daiichi Sankyo, Janssen, Merck, PDCline, Pfizer, Roche, Transgene; Financial Interests, Institutional, Invited Speaker: BMS, Pfizer. K. Cuppens: Financial Interests, Personal, Advisory Board: Hoffmann-La Roche, AstraZeneca, Pfizer, Merck Sharp Dohme, Bristol Myers Squibb, Pierre-Fabre Oncology, Amgen, Daiichi Sankyo, Janssen, Iteos therapeutics; Financial Interests, Personal, Expert Testimony: Merck Sharp Dohme, AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Sharp Dohme, Hoffmann-La Roche, Janssen, Merck Sharp Dohme. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi, Roche, Daichi Sankyo, Amgen, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Daiichi Sankyo, Sanofi, PDC line, Takeda, Amgen, Janssen. A. Sibille: Financial Interests, Institutional, Advisory Board: Merck Sharp Dome, AstraZeneca, Bristol Myers Squibb, Roche, Pfizer. M. Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Esai, 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, Expert Testimony, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee member: Lilly; Financial Interests, Institutional, Invited Speaker, Local PI: AbbVie, Amgen, Anheart Therapeutics, Apollomics, Arrivent Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Innate Pharma, Roche; Financial Interests, Institutional, Research Grant, Resarch grant: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Invited Speaker, Trial Chair: Anheart Therapeutics; Financial Interests, Personal, Invited Speaker, IDMC Chair: PharmaMar, Sophiagenetics; Financial Interests, Personal, Invited Speaker, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. D. Moro-Sibilot: Financial Interests, Personal, Advisory Board: Lilly, Roche, BMS, MSD, AbbVie, Becton Dickinson, Pfizer, Takeda, AstraZeneca, Boehringer Ingelheim, Novartis, GSK, SanofI; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Funding, IFCT clinical trials: Pfizer; Financial Interests, Institutional, Funding: Roche, AbbVie, AstraZeneca. F. Cantero, J. Plumas, F. Renard: Financial Interests, Personal, Sponsor/Funding: PDC*line pharma. All other authors have declared no conflicts of interest.