1397TiP - Phase III trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non-small cell lung cancer and secondary resistance to immunotherapy

Background

OSE2101 (TEDOPI®) is a therapeutic cancer vaccine composed of multiple peptides restricted to HLA-A2 phenotype targeting tumor-associated antigens (CEA, HER-2, MAGE-2, MAGE-3, P53) frequently expressed in non-small cell lung cancer (NSCLC). In prior studies, OSE2101 strongly induced T cell immune responses, with higher immune responses associated with longer survival (OS). In the randomized ATALANTE-1 study, OSE2101 significantly improved OS with a better safety profile and quality of life (QoL) compared to third-line chemotherapy (CT) in patients with NSCLC with progressive disease (PD) after at least 12-weeks of second line anti-PD(L)1 monotherapy. The aim of the phase III ARTEMIA study is to confirm the benefit of OSE2101 versus CT in second-line treatment of patients with NSCLC and secondary resistance to immune checkpoint inhibitor (ICI) given in the first line setting.

Trial design

HLA-A2 positive patients with metastatic NSCLC without known EGFR, ALK, ROS1 or other actionable alterations, no brain metastases, ECOG PS 0 or 1, who had PD ≥ 24 weeks after first line CT-ICI including at least 12 weeks of maintenance ICI without cytotoxic therapy, will be randomized 2:1 to receive either OSE2101 or docetaxel. Randomization will be stratified by histology (squamous vs non-squamous), and ECOG PS (0 or 1). Patients will receive subcutaneous OSE2101 every 3 weeks for 6 injections, then every 8 to 12 weeks up to end of year 2. In the control group, patients will receive docetaxel at 75 mg/m2 per standard of care. Primary endpoint is OS defined as time from randomization to death of any cause. Secondary endpoints include QoL Physical, Role, and Global Health Score by EORTC QLQ-C30 questionnaire, and time to ECOG PS deterioration. Assuming a hazard ratio of 0.70 with a power of 80% using a 2-sided log-rank test, 363 patients will be enrolled to reach 269 events. An interim analysis is planned. The ARTEMIA phase 3 study aims to confirm the benefit on survival and quality of life of the therapeutic cancer vaccine OSE2101 compared to docetaxel in second-line treatment of HLA-A2 positive patients with NSCLC and secondary resistance to immune checkpoint inhibitor.

Clinical trial identification

EU CT number: 2023-509340-10-00.

Editorial acknowledgement

Legal entity responsible for the study

OSE Immunotherapeutics.

Funding

OSE Immunotherapeutics.

Disclosure

S.V. Liu: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Daiichi Sankyo, Elevation Oncology, Genentech / Roche, Janssen, Jazz Pharmaceuticals, Merck, Novartis, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Catalyst, RAPT Therapeutics, Gilead, Guardant Health, Merus, Takeda, Revolution Medicines, Amgen, AbbVie, Boehringer Ingelheim, Mirati, Pfizer; Financial Interests, Institutional, Local PI: Alkermes, Elevation Oncology, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics, AbbVie, AstraZeneca, Puma; Financial Interests, Institutional, Steering Committee Member: Genentech; Financial Interests, Institutional, Coordinating PI: OSE Immunotherapeutics; Non-Financial Interests, Member: ASCO, IASLC. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Takeda, MSD, Bristol Myers-Squibb, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Local PI: MSD, Amgen, Celon Pharma, Pfizer, Novartis, Bristol Myers Squibb, Eli Lilly, Loxo; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Local PI: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche. S. Viteri: Financial Interests, Personal, Advisory Role: Roche, Bristol Myers Squibb, Janssen, Takeda, Reddy Pharma Iberia, Merck KGaA, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Roche, MSD, AstraZeneca Spain; Financial Interests, Personal, Other, Travel, accommodations: Roche, MSD, Merck KGaA. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD. S. Comis, C. Chevalier: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks or ownership: OSE Immunotherapeutics. V. Gabarre: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. T. Vandewalle: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics; Financial Interests, Personal, Other, Intellectual Property: Patent for OSE172: OSE Immunotherapeutics. F. Montestruc: Financial Interests, Personal, Member of Board of Directors, CEO of the company: eXYSTAT SAS; Financial Interests, Institutional, Other, Statistician Consultant: OSE immunotherapeutics, IFM, Bioprojet, Eurofins, Mapreg, Carely, PTC, CEVA, ARTIC, Orphelia, AbbVie; Financial Interests, Institutional, Other, Statistician consultant: Pfizer, Gensight, Geneuro, AbbVie, Biocodex, Imcheck, Takeda, Arcagy, Cureety; Non-Financial Interests, Other, Statistician consultant and Training: Institut Pasteur. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Other, Actions: OSE Immunotherapeutics. J. Remon Masip: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Merck, Takeda; Financial Interests, Personal, Other, Travel, accommodation: OSE Immunotherapeutics; Financial Interests, Institutional, Advisory Board: EDI MACK; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BeiGene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd., 4D Pharma, AbbVie, Da Voltera, Eli Lilly, Ellipse pharma Ltd., F-Star, GSK, Janssen, Onxeo, OSE Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD; Financial Interests, Institutional, Local PI: AbbVie, Amgen, Blueprint Medicines, Daiichi Sankyo, Pfizer, Roche-Genentech, Turning Point Therapeutics, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, OSE Immunotherapeutics, Sanofi, Taiho; Financial Interests, Institutional, Steering Committee Member: BeiGene, GSK, Janssen, Takeda, Genmab; Financial Interests, Institutional, Funding: Cristal Therapeutics.