PMID- 37704166 OWN - NLM STAT- MEDLINE DCOM- 20231002 LR - 20231015 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 34 IP - 10 DP - 2023 Oct TI - Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1. PG - 920-933 LID - S0923-7534(23)00790-1 [pii] LID - 10.1016/j.annonc.2023.07.006 [doi] AB - BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line >/=12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade >/=3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Besse, B AU - Besse B AD - Paris-Saclay University, Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France. Electronic address: Benjamin.BESSE@gustaveroussy.fr. FAU - Felip, E AU - Felip E AD - Oncology Department, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona. FAU - Garcia Campelo, R AU - Garcia Campelo R AD - Medical Oncology Department, Complejo Hospitalario Universitario A Coruna, Biomedical Research Institute, INIBIC, A Coruna. FAU - Cobo, M AU - Cobo M AD - Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain. FAU - Mascaux, C AU - Mascaux C AD - Pneumology Department, Hopitaux Universitaires de Strasbourg-Nouvel Hopital Civil, Strasbourg. FAU - Madroszyk, A AU - Madroszyk A AD - Medical Oncology Department, IPC-Institut Paoli-Calmettes, Marseille, France. FAU - Cappuzzo, F AU - Cappuzzo F AD - Oncology Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy. FAU - Hilgers, W AU - Hilgers W AD - Medical Oncology Department, Sainte Catherine Cancer Center, Avignon, France. FAU - Romano, G AU - Romano G AD - Medical Oncology Department, Ospedale Vito Fazzi-ASL Lecce, Lecce, Italy. FAU - Denis, F AU - Denis F AD - Medical Oncology Department, Institut Inter-Regional de Cancerologie Jean Bernard-Elsan, Le Mans, France. FAU - Viteri, S AU - Viteri S AD - Medical Oncology Department, Instituto Oncologico Dr. Rosell, Hospital Universitario Dexeus, Grupo Quironsalud, Barcelona, Spain. FAU - Debieuvre, D AU - Debieuvre D AD - Pneumology Department, Groupe Hospitalier de la Region Mulhouse Sud Alsace, Mulhouse, France. FAU - Galetta, D AU - Galetta D AD - Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari. FAU - Baldini, E AU - Baldini E AD - Oncology Department, Ospedale San Luca, Lucca, Italy. FAU - Razaq, M AU - Razaq M AD - Oncology Department, Stephenson Cancer Center, Oklahoma City, USA. FAU - Robinet, G AU - Robinet G AD - Oncology Department, Centre Hospitalier Regional Universitaire Morvan, Brest, France. FAU - Maio, M AU - Maio M AD - Department of Oncology, University of Siena and Center for Immuno-Oncology, University Hospital, Siena. FAU - Delmonte, A AU - Delmonte A AD - Thoracic Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST), Meldola, Italy. FAU - Roch, B AU - Roch B AD - Thoracic Oncology Unit, Montpellier University, University Hospital of Montpellier, Montpellier. FAU - Masson, P AU - Masson P AD - Pneumology Department, Centre Hospitalier de Cholet, Cholet, France. FAU - Schuette, W AU - Schuette W AD - Medical Oncology Department, Hospital Martha-Maria Halle-Doelau, Halle, Germany. FAU - Zer, A AU - Zer A AD - Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel. FAU - Remon, J AU - Remon J AD - Paris-Saclay University, Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France. FAU - Costantini, D AU - Costantini D AD - Medical Development Department, OSE Immunotherapeutics, Paris, France. FAU - Vasseur, B AU - Vasseur B AD - Medical Development Department, OSE Immunotherapeutics, Paris, France. FAU - Dziadziuszko, R AU - Dziadziuszko R AD - Oncology and Radiotherapy Department and Early Phase Clinical Trials Centre, Medical University of Gdansk, Gdansk, Poland. FAU - Giaccone, G AU - Giaccone G AD - Meyer Cancer Center, Weill Cornell Medicine, New York, USA. CN - ATALANTE-1 study group LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230911 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Cancer Vaccines) RN - 0 (HLA-A2 Antigen) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy MH - *Cancer Vaccines/adverse effects MH - HLA-A2 Antigen/therapeutic use MH - *Lung Neoplasms/drug therapy/etiology MH - Quality of Life MH - Treatment Outcome MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *COVID-19/etiology MH - Immunotherapy OTO - NOTNLM OT - advanced NSCLC OT - cancer vaccine OT - immunotherapy resistance OT - quality of life COIS- Disclosure BB: research funding, institution: Abbvie, Amgen, AstraZeneca, Chugai pharmaceutical, Daiichi-Sankyo, Ellipse pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar research, Taiho Oncology, Turning Point Therapeutics. EF: consulting or advisory role, personal: Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Pfizer, Sanofi, Takeda, Peptomyc, Daiichi Sankyo Europe GmbH, F. Hoffmann LaRoche, Merck Sharp & Dohme; speakers' bureau, personal: AstraZeneca, Bristol-Myers Squibb, Lilly, Medscape, Merck Sharp & Dohme, PeerVoice, Pfizer, Takeda, Amgen, F. Hoffmann LaRoche, Janssen, Medical Trends, Merck Serono, Sanofi, Touch ONCOLOGY; other relationship, personal: GRIFOLS; research funding, institution: Merck, Merck KGaA. RGC: consulting or advisory role, personal: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology; speakers' bureau, personal: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen, Lilly; travel, accommodations, expenses, personal: Roche/Genentech, MSD Oncology, Pfizer. CM: consulting or advisory role, personal: Roche, Sanofi, Takeda, Pfizer, Bristol-Myers Squibb, MSD, AstraZeneca, Kephren, AMGEN, Janssen, GlaxoSmithKline; honoraria, personal: Roche, AstraZeneca, Kephren, Bristol-Myers Squibb, Pfizer, Sanofi, MSD, Takeda, Janssen; travel, accommodations, expenses, personal: MSD; other, uncompensated relationships: Boehringer Ingelheim. FC: consulting or advisory role, personal: Roche/Genentech, AstraZeneca/MedImmune, Pfizer, Bristol-Myers Squibb, Takeda, Lilly, MSD Oncology, Bayer, Amgen, Sanofi, PharmaMar, Novocure; honoraria, personal: Pfizer, Roche/Genentech, AstraZeneca/MedImmune, Lilly, MSD Oncology, Bristol-Myers Squibb, Takeda, Bayer, Amgen, Sanofi, PharmaMar, Novocure; travel, accommodations, expenses, personal: OSE Immunotherapeutics. WH: consulting or advisory role, personal: AstraZeneca, Janssen; honoraria, personal: MSD Oncology. FD: consulting or advisory role, institution: SIVAN Innovation; honoraria, personal: AstraZeneca, MSD, Ipsen, Roche Belgium, Pfizer/EMD Serono, Takeda; stock and other ownership interests, institution: Kelindi; other relationship, personal: Takeda, Novartis, Ipsen, Janssen-Cilag, Merck Serono, Chugai Pharma, Ferring. SV: consulting or advisory role, personal: Roche; company: Bristol-Myers Squibb, Janssen, Takeda, Reddy Pharma Iberia, Merck KGaA, Puma Biotechnology; speakers' bureau, personal: Bristol-Myers Squibb, Roche, MSD, AstraZeneca Spain; travel, accommodations, expenses, personal: Roche, MSD, Merck KGaA. DD: consulting or advisory role, personal: BMS, OSE Immunotherapeutics, Amgen, AstraZeneca; honoraria, personal: AstraZeneca, BMS, Janssen, Amgen, Novartis, Sanofi Aventis, Ipsen, MSD, GSK, Hoffmann-La Roche, Pfizer, OSE Immunotherapeutics; research funding, institution: AstraZeneca, Chugai, Hoffmann-La Roche, Lilly, BMS, MSD, Boehringer-Ingelheim, Pfizer, Takeda, Bayer, Janssen, Sanofi-Aventis; travel, accommodations, expenses, personal: Amgen, BMS, AstraZeneca, MSD, Novartis, Roche, Pfizer, Janssen, Takeda. DG: consulting or advisory role, personal: Eli Lilly, Novartis, AZ, BMS, Pfizer; speakers' bureau, personal: Eli Lilly, Takeda, Novartis, BMS, MSD, Roche; travel, accommodations, expenses, personal: Amgen. GR: consulting or advisory role, personal: MSD, Astra Zeneca, BMS; honoraria, personal: Roche, MSD, Astra Zeneca; research funding, institution: Roche; travel, accommodations, expenses, personal: Roche, MSD, Astra Zeneca. MM: consulting or advisory role, personal: Alfasigma, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Incyte, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi; honoraria: Alfasigma, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, SciClone; stock and other ownership interests: Epigen Therapeutics, Theravance. AD: consulting or advisory role, personal: Novartis, Pfizer, Immunocore; research funding, institution: MSD; travel, accommodations, expenses, personal: MSD. BR: consulting or advisory role, personal: Amgen, AstraZeneca, BMS, Chugai, Lilly, Roche, Takeda; speaker's bureau: BMS, Roche; travel, accommodations, expenses, personal: BMS, Amgen, MSD, Roche, Novartis. WS: consulting or advisory role, personal: Roche, MSD, Novartis; honoraria, personal: Roche, MSD, Novartis. AZ: consulting or advisory role, personal: Boehringer Ingelheim, Roche, MSD, Oncotest/Rhenium, Lilly; honoraria, personal: MSD, Roche, AstraZeneca, Takeda, Novartis; stock and other ownership interests, personal: Nixio; research funding, institution: Bristol-Myers Squibb; travel, accommodations, expenses, personal: AstraZeneca, MSD, Roche. DC: employment, personal: OSE Immunotherapeutics; leadership, personal: OSE Immunotherapeutics; stock and other ownership interests, personal: OSE Immunotherapeutics. BV: employment, personal: OSE Immunotherapeutics; patents, royalties, other intellectual property, personal: uses of anti-SIRPa antibodies in the treatment of cancer; stock and other ownership interests, personal: OSE Immunotherapeutics. RD: consulting or advisory role, personal: Regeneron, Karyopharm Therapeutics; honoraria, personal: Roche/Genentech, Novartis, Pfizer, Bristol-Myers Squibb, Takeda, AstraZeneca, MSD Oncology, Boehringer Ingelheim, Seattle Genetics; travel, accommodations, expenses, personal: Roche, AstraZeneca. GG: consulting or advisory role, personal: Daiichi Sankyo, Novartis, Radiomics, Janssen Oncology, Sanofi, Eisai, Spectrum Pharmaceuticals, Sanofi/Regeneron; research funding, institution: MedImmune, Karyopharm Therapeutics, Cantargia AB; starting in September 2022, employee of Amgen. All other authors have declared no conflicts of interest. FIR - Zemanova, M IR - Zemanova M FIR - Besse, B IR - Besse B FIR - Bonnet, C IR - Bonnet C FIR - Cadranel, J IR - Cadranel J FIR - Chouaid, C IR - Chouaid C FIR - Cortot, A IR - Cortot A FIR - Debieuvre, D IR - Debieuvre D FIR - Delclaux, B IR - Delclaux B FIR - Denis, F IR - Denis F FIR - Duchemann, B IR - Duchemann B FIR - El Kouri, C IR - El Kouri C FIR - Ferrand, F R IR - Ferrand FR FIR - Ginoux, M IR - Ginoux M FIR - Hilgers, W IR - Hilgers W FIR - Madroszyk, A IR - Madroszyk A FIR - Masson, P IR - Masson P FIR - Mazieres, J IR - Mazieres J FIR - Molinier, O IR - Molinier O FIR - Moro-Sibilot, D IR - Moro-Sibilot D FIR - Pichon, E IR - Pichon E FIR - Mascaux, C IR - Mascaux C FIR - Robinet, G IR - Robinet G FIR - Roch, B IR - Roch B FIR - Zalcman, G IR - Zalcman G FIR - Schmidtke-Schrezenmeier, G IR - Schmidtke-Schrezenmeier G FIR - Schuette, W IR - Schuette W FIR - Urban, L IR - Urban L FIR - Gottfried, M IR - Gottfried M FIR - Nechushtan, H IR - Nechushtan H FIR - Peled, N IR - Peled N FIR - Wollner, M IR - Wollner M FIR - Zer, A IR - Zer A FIR - Baldini, E IR - Baldini E FIR - Bonanno, L IR - Bonanno L FIR - Bonetti, A IR - Bonetti A FIR - Cappuzzo, F IR - Cappuzzo F FIR - Delmonte, A IR - Delmonte A FIR - Galetta, D IR - Galetta D FIR - Maio, M IR - Maio M FIR - Minotti, V IR - Minotti V FIR - Rea, A IR - Rea A FIR - Romano, G IR - Romano G FIR - Tassinari, D IR - Tassinari D FIR - Tonini, G IR - Tonini G FIR - Dziadziuszko, R IR - Dziadziuszko R FIR - Karaszewska, B IR - Karaszewska B FIR - Szczesna, A IR - Szczesna A FIR - Cobo, M IR - Cobo M FIR - De Castro, J IR - De Castro J FIR - Felip, E IR - Felip E FIR - Garcia Campelo, M R IR - Garcia Campelo MR FIR - Hernandez, A IR - Hernandez A FIR - Moran, T IR - Moran T FIR - Provencio, M IR - Provencio M FIR - Viteri, S IR - Viteri S FIR - Dasgupta, A IR - Dasgupta A FIR - Gabrail, N IR - Gabrail N FIR - Giaccone, G IR - Giaccone G FIR - Harshad, A IR - Harshad A FIR - Liu, S IR - Liu S FIR - Oubre, D IR - Oubre D FIR - Panikkar, R IR - Panikkar R FIR - Razaq, M IR - Razaq M FIR - Sanborn, R IR - Sanborn R EDAT- 2023/09/14 00:42 MHDA- 2023/10/02 06:42 CRDT- 2023/09/13 19:18 PHST- 2023/04/04 00:00 [received] PHST- 2023/07/04 00:00 [revised] PHST- 2023/07/05 00:00 [accepted] PHST- 2023/10/02 06:42 [medline] PHST- 2023/09/14 00:42 [pubmed] PHST- 2023/09/13 19:18 [entrez] AID - S0923-7534(23)00790-1 [pii] AID - 10.1016/j.annonc.2023.07.006 [doi] PST - ppublish SO - Ann Oncol. 2023 Oct;34(10):920-933. doi: 10.1016/j.annonc.2023.07.006. Epub 2023 Sep 11.