ABSTRACT
Background: Tedopi® is an anticancer vaccine with modified neoepitopes restricted to HLA-A2+ targeting five tumor-associated antigens frequently expressed in lung cancer: CEA, HER2, MAGE2, MAGE3 and P53. ATALANTE-1 was a randomized, open-label, 2-Step phase 3 study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on ICI. Methods: HLA-A2+ NSCLC patients, EGFR and ALK negative, having progressed to platinum-based chemotherapy (CT) and anti-PD(L)1, ECOG PS 0-1 were randomized 2:1 to receive Tedopi® subcutaneously Q3W for 6 cycles, followed by maintenance Q8W up to first year, then Q12W, or SoC (docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W). The Step-1 hypotheses were based on the evaluation of 1y-OS rate (Fleming design: H0 futility boundary at 25%;H1 alternative efficacy: 40% of OS rate at 12 months). Step-2 was a superiority study with OS as primary endpoint. Results: At cutoff of February 2020, 99 patients (Tedopi® n=63;SoC n=36) were randomized and analyzable for Step-1. The 1y-OS was 29/63 (46%) [95%CI 33-59]) in Tedopi® group and 13/36 (36%) [95%CI 21-54] in SoC. The Step-1 endpoint has shown a lower limit of the 95% confidence interval above the futility boundary (25%) with an OS estimate of 10% above the estimate of SoC. Secondary endpoints and subgroup data will be further presented. Grade 3-4 related TEAEs were 11 % in Tedopi® group and 43 % in SoC. There was no related grade 5 TEAE. Related TEAE leading to withdrawal from the study were also less frequent in Tedopi® group (6%) versus SoC (14%). Due to the risk of COVID-19 pandemic on data integrity, following recommendation of the Independent Data Monitoring Committee and Steering Committee, the decision was taken to early terminate the study at Step-1 and definitely stop new accrual while continuing the OS follow-up in all patients. Conclusions: The Step-1 primary endpoint was positively achieved with a 1y-OS rate of 46% and a good safety profile. Step-1 results shown a favorable benefit/risk of Tedopi® over SoC as 2nd or 3rd line treatment in advanced HLA-A2+ NSCLC patients after failure to ICI. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Legal entity responsible for the study: OSE Immunotherapeutics. Funding: OSE Immunotherapeutics. Disclosure: G. Giaccone: Advisory/Consultancy: CStone;Advisory/Consultancy: Novartis;Advisory/Consultancy: Daiichi;Research grant/Funding (institution): Medimunne;Research grant/Funding (institution): Incyte. E. Felip: Advisory/Consultancy: AbbVie;Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy: Blueprint Medicine;Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim;Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Advisory/Consultancy, Speaker Bureau/Expert testimony: Elli Lilly;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Janssen;Advisory/Consultancy: Merck KgaA;Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD;Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Advisory/Consultancy: GSK;Advisory/Consultancy: Bayer;Speaker Bureau/Expert testimony: Medscape;Speaker Bureau/Expert testimony: Prime Oncology;Speaker Bureau/Expert testimony: Touchime;Research grant/Funding (institution): Fundation Merck Salud;Advisory/Consultancy: Grifols. R. Garcia Campelo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;H noraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. F. DENIS: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: Shugai;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Bayer;Advisory/Consultancy: MSD;Advisory/Consultancy, Licensing/Royalties: Sivan. E. Quoix: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony: Shugai;Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: Takeda;Honoraria (self), interview at ASCO 2019: Medscape. A. Madroszyk: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: MSD. D. Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD;Honoraria (self), Research grant/Funding (institution): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self): Shugai;Advisory/Consultancy, Research grant/Funding (institution): Pfizer;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Research grant/Funding (institution): Lilly;Research grant/Funding (institution): Sandoz;Travel/Accommodation/Expenses: Boehringer Ingelheim. W. Hilgers: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self): MSD;Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen;Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas;Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Roche. T. Moran: Advisory/Consultancy: Roche;Advisory/Consultancy: Boehringer Ingelheim. D. Galetta: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca. F. Cappuzzo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. G. Robinet: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZenaca;Advisory/Consultancy: BMS. S. Viteri: Full/Part-time employment: Pangaea Oncology;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie;Honoraria (self), Travel/Accommodation/Expenses: MSD;Research grant/Funding (institution), Travel/Accommodation/Expenses: Ose Immunotherapeutics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KgaA;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Boston Pharmaceuticals Research grant/Funding (institution): Exelexis;Research grant/Funding (institution): Novocure;Research grant/Funding (institution): MedImmune. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Foundation Medicine;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardian 360;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genesort;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck KgaA;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NovellusDx;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. D. Costantini: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: OSEImmunotherapeutics. R. Dziadziuszko: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self): Pfizer;Honoraria (self): Novartis;Honoraria (self): MSD;Honoraria (self): Foundation Medicine;Honoraria (self), Advisory/Consultancy: Takeda;Advisory/Consultancy: Seattle Genetics. B. Besse: Research grant/Funding (institution): AbbVie;Research grant/Funding (institution): Amgen;Research grant/Funding (institution): AstraZeneca;Research grant/Funding (institution): Beigene;Research grant/Funding (institution): Blueprint Medicine;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Cellgene;Research grant/Funding (institution): Cristal Therapeutics;Research grant/Funding (institution): Daichi-Sankyo;Research grant/Funding (institution): Elli-Lilly;Research grant/Funding (institution): GSK;Research grant/Funding (institution): Ignyta;Research grant/Funding (institution): Ipsen;Research grant/Funding (institution): Inivata;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Merck KgaA;Research grant/Funding (institution): MSD;Research grant/Funding (institution): Nektar;Research grant/Funding (institution): Onxeo;Research grant/Funding (institution): Ose Immunotherapeutics;Research grant/Funding (institution): Pfizer;Research grant/Funding (institution): PharmaMar;Research grant/Funding (institution): Roche-Genentech;Research grant/Funding (institution): Sanofi;Research grant/Funding (institution): Servier;Research grant/Funding (institution): Spectrum Pharmaceuticals;Research grant/Funding (institution): Takeda;Research grant/Funding (institution): Tiziana Pharma;Research grant/Funding (institution): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.