830TiP - A randomized phase II study of maintenance therapy with multiepitope vaccine tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM – PRODIGE 63 GERCOR study)

Abstract

BackgroundFOLFIRINOX (5FU, folinic acid [FA], irinotecan [Iri], oxaliplatin [Ox]) is a 1st-line standard in fit Pts with aPDAC. Anti-PD-(L)1 as single agents have failed in aPDAC and new combination immunotherapies are needed. Tedopi (OSE2101) is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts targeting 5 tumor-associated antigens (ACE, HER2, MAGE2, MAGE3, TP53) frequently expressed in PDAC. This study aims to assess the efficacy and safety of Tedopi alone and in combination with anti-PD-1 nivolumab or FOLFIRI as maintenance therapy in aPDAC Pts after FOLFIRINOX induction CT. Trial designTEDOPaM is a 3-arm, Fleming 2-stage, open-label, randomized, non-comparative phase II study. 156 Pts with recurrent or advanced, pathologically proven PDAC; ECOG PS 0-1; HLA-A2 genotype; controlled disease (PR or SD) after 8 cycles of FOLFIRINOX; adequate organ functions, are randomized (1:1:1, stratified on center, tumor stage, best response to FOLFIRINOX) into 3 arms:Table830TiPTableArm A (reference): FOLFIRI (n=52)IV; FA 400mg/m2, Iri 180mg/m2, 5FU bolus 400mg/m2 + continuous 2400mg/m2/46hArm B: Tedopi (n=52)Subcutaneous injection on D1 Q3W/6 doses then Q8W until month 12 [M12] then Q12W up to M24Arm C: Tedopi + nivolumab (n=52)Tedopi + nivolumab 360mg IV on D1 Q3W/6 doses then 480mg Q4W up to M24In Arms B and C, reintroduction of FOLFIRI at disease progression or unacceptable toxicity. Primary endpoint: overall survival rate at M12. Secondary: progression-free survival (CT-scan Q8W), duration of disease control, safety, response rate, RECIST v1.1/iRECIST comparison, HRQoL, Q-TWiST. Interim analysis after inclusion of 20 Pts in each arm. Translational research on tumor tissue (initial FFPE biopsy and optional re-biopsy at inclusion): RNAseq (cancer and stroma), mutation burden, MMR status, immune infiltrates; and in blood (before and on-treatment): cytokine panel, PBMC phenotyping, vaccine-antigen specific T-cells, TCR repertoire, extracellular vesicles to explore biomarkers and pharmacodynamics effects of Tedopi ± nivolumab. Clinical trial identificationNCT03806309. Legal entity responsible for the studyGERCOR. FundingOSE Immunotherapeutics. DisclosureC. Neuzillet: Honoraria (self), Not related to the abstract: Amgen; Honoraria (self), Not related to the abstract: AstraZeneca; Research grant / Funding (institution), Not related to the abstract: Celgene; Honoraria (self), Travel / Accommodation / Expenses, Not related to the abstract: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses, PI of the TEDOPaM Clinical Trial: OSE Immunotherapeutics; Honoraria (self), Not related to the abstract: Roche; Honoraria (self), Not related to the abstract: Servier. V. Hautefeuille: Honoraria (self), Not related to the abstract: Amgen; Honoraria (self), Not related to the abstract: Novartis; Honoraria (self), Not related to the abstract: Ipsen; Honoraria (self), Not related to the abstract: Pfizer; Honoraria (self), Not related to the abstract: AAA; Honoraria (self), Not related to the abstract: Sanofi; Honoraria (self), Not related to the abstract: Merck; Honoraria (self), Not related to the abstract: Servier; Honoraria (self), Not related to the abstract: Lilly. A. Lambert: Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy: Bayer; Honoraria (self): Servier/Pfizer. D. Vernerey: Advisory / Consultancy: OSE Immunotherapeutics; Advisory / Consultancy: HalioDX; Advisory / Consultancy: Pfizer; Advisory / Consultancy: CellProthera. All other authors have declared no conflicts of interest.