1260MO - 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

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 2^nd or 3^rd 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.

Editorial acknowledgement

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; Honoraria (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: OSE Immunotherapeutics. 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.