P2.06-024 Tedopi vs Standard Treatment as 2nd or 3rd Line in HLA-A2 Positive Advanced NSCLC Patients in a Phase 3, Randomized Trial: ATALANTE-1: Topic: Phase III

Abstract

HLA-A2 is expressed in 40 to 50% of NSCLC patients. TEDOPI is a combination of neoepitopes that generates cytotoxic T lymphocytes responses. It consists of nine HLA-A2 supertype binding epitopes covering five tumor-associated antigens overexpressed in advanced NSCLC and the universal helper pan-DR epitope. In a phase II trial (NCT00104780, Barve et al. JCO 2008), TEDOPI showed a promising median overall survival of 17.3 months with a manageable safety profile in pre-treated HLA-A2 positive patients with advanced NSCLC. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase 3 study comparing the efficacy and safety of TEDOPI with standard treatment in HLA-A2 positive patients with advanced NSCLC, as second- or third-line therapy. Section not applicable. Trial design: Patients with advanced NSCLC without EGFR-sensitizing mutations or ALK rearrangements, with progressive disease to first-line platinum-based chemotherapy or second-line immune checkpoint inhibitors (IC) are eligible if they have HLA-A2 positivity and ECOG PS 0-1. Treated and asymptomatic brain metastases are allowed. Patients are randomized 1:1 to receive 1 ml TEDOPI subcutaneously Q3W for 6 cycles, then every two months for the reminder of the year and finally every three months or standard treatment with: 75 mg/m2 docetaxel Q3W or 500 mg/m2 pemetrexed Q3W (in non-squamous histology and pemetrexed-naïve patients). In both arms, treatment continues until progression, intolerable toxicity, consent withdrawal, or investigator decision. In TEDOPI arm, treatment may continue beyond initial radiographic disease progression in case of clinical benefit. Randomization is stratified by histology (squamous vs. non-squamous), initial response to first-line chemotherapy (partial or complete response vs. stabilization or progression), and previous treatment with IC (yes vs. no). Tumor assessment is performed every 6 weeks and adverse events are collected throughout the study and for 60 days and 90 days thereafter and graded per NCI CTCAE v4.0. Archival biopsies samples are required for assessing PD-L1 status (IHC22C3 pharmDx from Dako). Primary endpoint is overall survival; and secondary are progression free survival based on RECIST 1.1 criteria, objective response rate, disease control rate, duration of response, and quality of life measured by QLQ-C30 and QLQ-LC13 global scores. This is a superiority study with a hazard ratio of 0.7391, two-sided alpha 5% and power 80%, after 356 events are observed over 500 patients. The first patient was enrolled on 25th January 2016. Enrolment is ongoing in Europe and the US. Clinical trial identification: NCT02654587 Legal entity responsible for the study & Funding: OSE Immunotherapeutics, France. Section not applicable.