1487TiP - A randomized non-comparative phase II study of maintenance therapy with FOLFIRI alone or in combination with Tedopi vaccine after induction therapy with FOLFIRINOX in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (TEDOPAM – D17-01 PRODIGE 63 STUDY)

Background

Tedopi (OSE2101) is a multiple neoepitope vaccine restricted to HLA-A2 positive patients (Pts) targeting 5 tumor-associated antigens (ACE, HER2, MAGE2, MAGE3, TP53) frequently expressed in pancreatic ductal adenocarcinoma (PDAC). The TEDOPaM - PRODIGE 63 aims to assess the efficacy and safety of Tedopi in advanced PDAC Pts after FOLFIRINOX induction chemotherapy (CT). It was initially a randomized, non-comparative phase II study with 3 arms: FOLFIRI, Tedopi, Tedopi + nivolumab. Following the IDMC meeting in July 2020 (N=29 Pts), suggesting that early CT discontinuation may be deleterious, Sponsor decided to stop the evaluation of Tedopi without CT and maintain a CT backbone with FOLFIRI.

Trial design

TEDOPAM is now a 2-arm, two-stage, open-label, randomized, non-comparative phase II study. Pts with recurrent or advanced, pathologically proven PDAC, ECOG PS 0-1, HLA-A2 genotype and controlled disease after a 4-month (8 cycles) induction course of chemotherapy with FOLFIRINOX or modified FOLFIRINOX are randomized (1:1, stratified on center, tumor stage, best response to FOLFIRINOX) into one of the 2 arms (N=53 Pts/arm): - Arm A (reference arm): maintenance with FOLFIRI (folinic acid 400 mg/m², irinotecan 180 mg/m², 5FU bolus 400 mg/m² + continuous 2400 mg/m²/46h) - Arm B (experimental arm): maintenance with FOLFIRI + OSE2101 (subcutaneous injection on D1 Q3W/6 doses then Q8W until M12 then Q12W up to M24) FOLFIRI in both arms is until disease progression or unacceptable toxicity. Primary endpoint: overall survival rate at M12. Secondary: progression-free survival (CT-scan Q8W), safety, response rate and quality of life. Interim analysis after inclusion of 20 Pts in each arm. Translational research to explore prognostic and predictive biomarkers on tumor tissue (initial biopsy and optional re-biopsy at inclusion): RNAseq, mutation burden, immune infiltrates; and in blood (before and on-treatment): cytokine panel, vaccine-antigen specific T-cells, extracellular vesicles.

Clinical trial identification

NCT03806309.

Editorial acknowledgement

Legal entity responsible for the study

GERCOR.

Funding

OSE Immunotherapeutics.

Disclosure

V. Hautefeuille: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Lilly. A. Lambert: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Servier. D. Vernerey: Financial Interests, Personal, Advisory Board: OSE Immunotherapeutics; Financial Interests, Personal, Advisory Board: HalioDX; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: CellProthera. C. Neuzillet: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Principal Investigator: OSE Immunotherapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Servier. All other authors have declared no conflicts of interest.