LBA47 - Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): Final results of phase III Atalante-1 randomised trial

Background

OSE2101 (Tedopi®) is an anticancer vaccine (modified epitopes restricted to HLA-A2+ from 5 tumor-associated antigens). Atalante-1 is a randomized phase 3 trial of OSE2101 vs Standard of Care (SoC docetaxel or pemetrexed) in pretreated HLA-A2+ patients with advanced NSCLC, with IO as last treatment.

Methods

EGFR and ALK negative NSCLC patients, ECOG PS 0-1 were randomized 2:1 to receive OSE2101 subcutaneously Q3W for 6 cycles, followed by maintenance Q8W for 1 year and Q12W until progression, versus SoC (docetaxel or pemetrexed Q3W). Primary endpoint was OS (initial hypothesis of HR 0.7 for 401 pts). Secondary endpoints were disease control rate (DCR), quality of life (QoL - EORTC QLQ-C30/LC13), and Progression free survival (PFS). Toxicities were reported using CTCAE 5.0. Positive pre-specified analyses (ESMO 2020 #1260MO) identified a Population of Interest (PoI) comprised by patients with IO secondary resistance defined as failure after a minimum of 12 weeks IO in sequential CT-IO patients. Due to the risk of COVID-19 pandemic on data integrity, the study was stopped prematurely following IDMC recommendations. PoI was chosen as primary population for the final analysis.

Results

219 pts were enrolled: median age 65 years, 29% female, 10% never-smoker, 70% non-squamous. 183 (84%) pts received sequential CT-IO from whom 118 pts (54%) complied with the definition of PoI, with otherwise similar characteristics that the overall population. In PoI, mOS was 11.1 mo for OSE2101 vs 7.5 for SoC [HR 0.59 (0.38-0.91) p= 0.02]. 6 mo-DCR 25% vs 24% (NS), mPFS 2.7 mo vs 3.4 (NS), ORR 8% vs 18% (p=0.07). Post progression survival was 7.7 mo vs 4.6 [HR 0.46 p= 0.004], time to worsening ECOG PS 8.6 mo vs 3.3 [HR 0.45 p= 0.0005]. In the total population, HR for OS was 0.86 (0.62-1.19) p=0.36. QoL Global Health Status was maintained for OSE2101 (p<0.05). Severe Adverse Events were 38% vs 68% (p<0.001). There was no TEAE of concern in the OSE2101 group.

Conclusions

OSE2101 had a favorable benefit/risk of versus SoC in advanced HLA-A2+ NSCLC patients. HR for OS improved from 0.86 to 0.59 in patients with secondary resistance to IO with a meaningful gain of median OS of 3.6 months with OSE2101.

Clinical trial identification

EudraCT 2015-003183-36; NCT02654587.

Editorial acknowledgement

We thank Pierre Attali (Medical Expert, MD), François Montestruc (Statistics, eXYSTATt) and Berangere Vasseur (MD, OSE Immunotherapeutics) for their support in the writing of the abstract.

Legal entity responsible for the study

OSE Immunotherapeutics.

Funding

OSE Immunotherapeutics.

Disclosure

B. Besse: Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BEIGENE; Financial Interests, Institutional, Research Grant: Blue Print Medicines; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Cellgene; Financial Interests, Institutional, Research Grant: Cristal Therapeutics; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Inivata; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Onxeo; Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche-Genentech; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: 4D Pharma; Financial Interests, Institutional, Research Grant: Aptitude Health; Financial Interests, Institutional, Research Grant: Cergentis. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bristol-Myers; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Bristol-Myers; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Bristol-Myers; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Janssen. E. Quoix: Financial Interests, Personal, Speaker’s Bureau: Shugaï; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: OSE Immunotherapeutics; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: GSK. E. Felip: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Medical Trends; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: PEPTOMYC; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Syneos Health; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Medscape; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Personal, Speaker’s Bureau: PeerVoice; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Springer; Financial Interests, Personal, Speaker’s Bureau: Touch Medical; Financial Interests, Personal, Other, Independent Member of the Board: Grifols; Non-Financial Interests, Institutional, Research Grant: Grant For Oncology Innovation (GOI); Non-Financial Interests, Institutional, Research Grant: Fundación Merck Salud. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AZ; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Sanofi. F. Denis: Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche. W. Hilgers: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD. S. Viteri: Financial Interests, Personal, Full or part-time Employment: Pangaea Oncology; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Boston Pharmaceuticals; Financial Interests, Institutional, Research Grant: Exelexis; Financial Interests, Institutional, Research Grant: Novocure; Financial Interests, Institutional, Research Grant: Medimmune; Financial Interests, Personal, Other, Travel accomodation expenses: Roche; Financial Interests, Personal, Other, Travel accomodation expenses: Merck; Financial Interests, Personal, Other, Travel accomodation expenses: MSD; Financial Interests, Personal, Other, Travel accomodation expenses: BMS; Financial Interests, Personal, Other, Travel accomodation expenses: OSE Immunotherapeutics. W. Schuette: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck. A. Zer: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Stocks/Shares: Nixio; Non-Financial Interests, Institutional, Research Grant: BMS. D. Costantini: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Role: F. Hoffman- La Roche Ltd; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Foundation Medicine Takeda; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Principal Investigator: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme; Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Personal, Principal Investigator: Janssen; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Product Samples: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Institutional, Product Samples: Novartis; Non-Financial Interests, Institutional, Product Samples: Pfizer. All other authors have declared no conflicts of interest.