Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): Step 1 results of phase III ATALANTE-1 randomised trial

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 21 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.