ATALANTE-1 randomized phase III trial, OSE-2101 versus standard treatment as second or third-line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients

Abstract

Background: Moving immune checkpoint inhibitors (ICI) in first-line setting in advanced NSCLC, new treatment strategies are needed for patients who progress on treatment with ICI. Tedopi® (OSE-2101) is a neoepitope vaccine restricted to HLA-A2 positive patients (∼45% of NSCLC) targeting five tumor-associated antigens expressed in lung cancer cells: ACE, HER2, MAGE2, MAGE3 and P53. In a phase II trial (Barve et al. JCO 2008), Tedopi® showed a median overall survival (OS) of 17.3 months with a manageable safety profile in pre-treated advanced NSCLC patients. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase III study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2 positive patients with advanced NSCLC after progression on ICI. Trial design: Patients with advanced NSCLC (EGFR and ALK negative), progressive disease to platinum-based chemotherapy with sequential or concurrent ICI, HLA-A2 positivity (blood test), ECOG PS 0-1, treated and asymptomatic brain metastases allowed, are randomized 2:1 to receive 1 ml Tedopi® subcutaneously Q3W for 6 cycles, then Q8W for the remainder of the year and finally Q12W, or SoC treatment (docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W). In both arms, treatment continues until progression, intolerable toxicity or consent withdrawal. Stratification criteria are histology, best response to first-line, line rank of ICI. Tumor assessment is performed every 6 weeks (RECIST 1.1). Primary endpoint is OS; Secondary endpoints are: Progression Free Survival, Objective Response Rate , Disease Control Rate , Duration of response, Quality of Life and safety. This is a superiority study with a hazard ratio of 0.7, two-sided alpha 5% and power 80%, after 278 events are observed. An independent analysis (1y-OS rate) is planned in the first 84 patients treated with Tedopi® . Last study review by the Data Monitoring Committee in June 18 suggested that the study continues as planned. Translational research will evaluate pharmacodynamic markers of efficacy baseline and after treatment initiation in this population of NSCLC patients who progressed after ICI treatment.