Philippe JEAN-PIERRE

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• Type de publi. : Rapport
• Date de publi. : 06/11/2023
• Auteurs : Nicolas Danel-BuhlAlain BoissonnasPatricia BoltzPascal CrennLouise GaboriauLaetitia Jacquesson-FournolsRaymond JianGisèle KannyLaetitia Koppe-GuichardMartine MorissetRuddy RichardFanny RocherPhilippe SchererJean-Fabien ZazzoClara Benzi-SchmidKarine Adel-PatientCharlotte BeaudartAnnabelle BedardCécile BetryPatrick BorelBlandine de Lauzon-GuillainChristine Feillet-CoudrayJerome Gay-QueheillardAurélie GoncalvesTao JiangEmmanuelle Kesse-GuyotNathanaël LapidusCorinne Malpuech BrugèreChristine MorandThomas MouillotRuddy RichardAnne-Sophie RousseauOlivier SteichenStéphane WalrandVincent BitaneAymeric DopterClaire MathiotAurélien Mondier CasiniPerrine Nadaud
• Organismes : GHT de l'Artois Université Paris-Sud - Paris 11 - Faculté de médecine Centre Hospitalier Régional Universitaire de Nancy GHU AP-HP. Université Paris Saclay Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] Clinique de la Muette Hôpital Européen Georges Pompidou [APHP] Centre Hospitalier Universitaire de Nancy Hospices Civils de Lyon Centre Hospitalier Universitaire d'Angers Université Clermont Auvergne CHU Nice [Cimiez] Retraité AP-HP - Hôpital Antoine Béclère [Clamart] Office fédéral de la sécurité alimentaire et des affaires vétérinaires Université Paris-Saclay CEA- Saclay Université de Liège = University of Liège = Universiteit van Luik = Universität Lüttich Centre de recherche en épidémiologie et santé des populations Institut cellule souche et cerveau / Stem Cell and Brain Research Institute Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research Université Paris Cité Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques Dynamique du Muscle et Métabolisme Périnatalité et Risques Toxiques - UMR INERIS_I 1 UPJV Nîmes Université Laboratoire Activités Physiques et Sportives et processus PSYchologiques : recherches sur les Vulnérabilités - Nîmes Université Université de Bourgogne Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle Institut Pierre Louis d'Epidémiologie et de Santé Publique Université Clermont Auvergne Département Alimentation Humaine - INRAE Unité de Nutrition Humaine Unité de Nutrition Humaine Université Clermont Auvergne Université Bourgogne Franche-Comté [COMUE] Centre des Sciences du Goût et de l'Alimentation [Dijon] Université Clermont Auvergne Institut de Biologie Valrose Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Tenon [AP-HP] Unité de Nutrition Humaine Université Clermont Auvergne Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques

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Résumé : Dans le cadre de son dispositif de nutrivigilance créé en 2009, l’Anses a reçu 9 signalements d’effets indésirables susceptibles d’être liés à la consommation des produits de nutrition entérale (NE) Fresubin 2kcal HP Fibre® ou de Fresubin 2 kcal HP® commercialisés en France par la société Fresenius Kabi. Parmi ceux-ci, 8 rapportaient des effets ayant une sévérité de niveau 3 (dont 2 avec menace du pronostic vital) et 1 rapportait un effet ayant une sévérité de niveau 41. Ces cas, enregistrés dans la base de données de nutrivigilance sous les numéros 2022-250, 023-013,2023-014, 2023-15, 2023-066, 2023-102, 2023-103 et 2023-105 ont été jugés d’imputabilité très vraisemblable et le cas 2023-104 a été jugé d’imputabilité vraisemblable. Etant donné la sévérité des effets indésirables rapportés, l’Anses a estimé nécessaire de porter ces cas à la connaissance des professionnels de santé et du public, dans un but d’amélioration de la sécurité de leur utilisation et s’est autosaisie le 17 octobre 2022.

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• Type de publi. : Article dans une revue
• Date de publi. : 06/11/2023
• Auteurs : Sylvain GoutelleVincent JullienJean-Pierre BruVincent CattoirRémy GauzitPhilippe LespritGérard LinaFrédéric SchrammEtienne CanouiOlivier Chosidow
• Organismes : Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Hospices Civils de Lyon Université Sorbonne Paris Nord Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] ARN bactériens et médecine AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Centre International de Recherche en Infectiologie Fédération de Médecine Translationnelle de Strasbourg CHU Henri Mondor [Créteil]
• Publié dans Journal of Antimicrobial Chemotherapy le 31/10/2020

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Résumé : Background: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).Methods: Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.Results: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.Conclusions: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.

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Fichiers liés : GOUTELLE et al-2023-Defining standard and high dosages for beta-lactam agents administered .pdf

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 03/11/2023
• Auteurs : Chloé BeaulieuCyril LibourelDuchesse Lacourt Mbadinga ZamarKarima El MahboubiDavid HoeyJean KellerCamille GirouHélène San ClementeIssa DiopEmilie AmblardAnthony ThéronStephane CauetNathalie RoddeSabine ZachgoWiebke HalpapeAnja MeierhenrichBianca LakerAndrea BräutigamGeorge Rl GreiffPeter SzovenyiShifeng ChengYasuhiro TanizawaJames Leebens-MackJeremy SchmutzJenel WebberJane GrimwoodChristophe JacquetChristophe DunandJessica NelsonFabrice RouxHervé PhilippeSebastian SchornackMaxime BonhommePierre-Marc Delaux
• Organismes : Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Sainsbury Laboratory Cambridge University Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Universität Zürich [Zürich] = University of Zurich Zurich Basel Plant Science Center LRSV-Evolution des Interactions Plantes-Microorganismes Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales University of Osnabrueck = Osnabrueck Universität Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Sainsbury Laboratory Cambridge University Universität Zürich [Zürich] = University of Zurich Zurich Basel Plant Science Center Chinese Academy of Agricultural Sciences National Institute of Genetics [Shizuoka, Japan] University of Georgia [USA] HudsonAlpha Institute for Biotechnology [Huntsville, AL] Lawrence Berkeley National Laboratory [Berkeley] HudsonAlpha Institute for Biotechnology [Huntsville, AL] HudsonAlpha Institute for Biotechnology [Huntsville, AL] LRSV-Evolution des Interactions Plantes-Microorganismes LRSV-Dynamique et Evolution des Parois cellulaires végétales Maastricht University [Maastricht] Laboratoire des Interactions Plantes Microbes Environnement Station d'Ecologie Théorique et Expérimentale National Institute of Genetics [Shizuoka, Japan] Sainsbury Laboratory Cambridge University LRSV-Evolution des Interactions Plantes-Microorganismes LRSV-Evolution des Interactions Plantes-Microorganismes

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Résumé : Plant adaptation to a terrestrial life 450 million years ago played a major role in the evolution of life on Earth. This shift from an aquatic environment has been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the non-vascular plants Marchantia polymorpha and studied its intraspecific diversity using selection signature analyses, genome-environment association study and a gene-centered pangenome. We identified adaptive features shared with flowering plants, such as peroxidases or nucleotide-binding and leucine-rich repeat (NLR), which likely played a role in the adaptation of the first land plants to the terrestrial habitat. The M. polymorpha pangenome also harbored lineage-specific accessory genes absent from seed plants. We conclude that different land plants lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage specific polymorphisms and gene family evolutions.

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• Type de publi. : Article dans une revue
• Date de publi. : 02/11/2023
• Auteurs : Martin SchwartzPhilippe CiaisAurelien de TruchisJérôme ChaveCatherine OttleCedric VegaWigneron J.-P.Manuel NicolasSami JouaberSiyu LiuMartin BrandtIbrahim Fayad
• Organismes : Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Kayrros Evolution et Diversité Biologique Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Modélisation des Surfaces et Interfaces Continentales IGN-France International Interactions Sol Plante Atmosphère Réseau national de suivi à long terme des écosytèmes forestiers Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] IT University of Copenhagen IT University of Copenhagen Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Kayrros
• Publié dans Earth System Science Data le 23/10/2020

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Résumé : The contribution of forests to carbon storage and biodiversity conservation highlights the need for accurate forest height and biomass mapping and monitoring. In France, forests are managed mainly by private owners and divided into small stands, requiring 10 to 50 m spatial resolution data to be correctly separated. Further, 35 % of the French forest territory is covered by mountains and Mediterranean forests which are managed very extensively. In this work, we used a deep-learning model based on multi-stream remote-sensing measurements (NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission and ESA's Copernicus Sentinel-1 and Sentinel-2 satellites) to create a 10 m resolution canopy height map of France for 2020 (FORMS-H). In a second step, with allometric equations fitted to the French National Forest Inventory (NFI) plot data, we created a 30 m resolution above-ground biomass density (AGBD) map (Mg ha−1) of France (FORMS-B). Extensive validation was conducted. First, independent datasets from airborne laser scanning (ALS) and NFI data from thousands of plots reveal a mean absolute error (MAE) of 2.94 m for FORMS-H, which outperforms existing canopy height models. Second, FORMS-B was validated using two independent forest inventory datasets from the Renecofor permanent forest plot network and from the GLORIE forest inventory with MAE of 59.6 and 19.6 Mg ha−1, respectively, providing greater performance than other AGBD products sampled over France. Finally, we compared FORMS-V (for volume) with wood volume estimations at the ecological region scale and obtained an R2 of 0.63 with an MAE of 30 m3 ha−1. These results highlight the importance of coupling remote-sensing technologies with recent advances in computer science to bring material insights to climate-efficient forest management policies. Additionally, our approach is based on open-access data having global coverage and a high spatial and temporal resolution, making the maps reproducible and easily scalable. FORMS products can be accessed from https://doi.org/10.5281/zenodo.7840108 (Schwartz et al., 2023).

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Fichiers liés : essd-15-4927-2023.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 02/11/2023
• Auteurs : Laurence BuisseretDelphine LoiratPhilippe AftimosChristian MaurerKevin PunieVéronique DebienPaulus KristantoDaniel EigerAnthony GoncalvesFrançois GhiringhelliDonatienne TaylorFlorent ClatotTom van den MooterJean-Marc FerreroHervé BonnefoiJean-Luc CanonFrancois DuhouxLaura MansiRenaud PoncinPhilippe BarthélémyNicolas IsambertZoë DenisXavier CatteauRoberto SalgadoElisa AgostinettoEvandro de AzambujaFrançoise RothéLigia CraciunDavid VenetEmanuela RomanoJohn StaggMarianne PaesmansDenis LarsimontChristos SotiriouMichail IgnatiadisMartine Piccart
• Organismes : Université libre de Bruxelles = Free University of Brussels Hôpital Universitaire de Bruxelles Institut Jules Bordet [Bruxelles] Institut Curie [Paris] Institut Jules Bordet [Bruxelles] Universitair Ziekenhuis Leuven = University Hospital of Leuven = Hopital universitaire de Louvain Institut de Cancérologie de Strasbourg Europe Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] Institut Paoli-Calmettes Département d'oncologie médicale [Centre Georges-François Leclerc] Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] BoRdeaux Institute of onCology Centre Hospitalier Universitaire de Charleroi-Chimay Université de Franche-Comté - Centre de formation universitaire en orthophonie Saint Pierre clinic of Ottignies Institut de Cancérologie de Strasbourg Europe
• Publié dans Nature Communications le 23/10/2020

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Résumé : Abstract Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B ( p = 0.90). The safety profile was manageable in both arms.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Tae Won KimPhilippe BedardPatricia LorussoMichael GordonJohanna BendellDo-Youn OhMyung-Ju AhnElena GarraldaSandra D’angeloJayesh DesaiF. Stephen HodiZev WainbergJean-Pierre DelordPhillippe CassierAndrés CervantesMarta Gil-MartinBenjamin WuNamrata PatilYanling JinTien HoangDiana MendusXiaohui WenRaymond MengByoung Chul Cho
• Organismes : University of Ulsan Princess Margaret Hospital Yale School of Medicine [New Haven, Connecticut] HonorHealth Research and Innovation Institute, Scottsdale, Arizona. F. Hoffmann-La Roche [Basel] Sarah Cannon Research Institute [Nashville, Tennessee] Seoul National University College of Medicine [Séoul, Corée du Sud] Samsung Medical Center Sungkyunkwan University School of Medicine Vall d'Hebron University Hospital [Barcelona] Memorial Sloan Kettering Cancer Center Weill Medical College of Cornell University [New York] Peter MacCallum Cancer Centre Dana-Farber Cancer Institute [Boston] Jonsson Comprehensive Cancer Center Institut Universitaire du Cancer de Toulouse - Oncopole Centre Léon Bérard [Lyon] Universitat de València = University of Valencia = Universidade de Valencia Catalan Institute of Oncology [Girona] Genentech, Inc. Genentech, Inc. F. Hoffmann-La Roche [Basel] Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc. Yonsei Cancer Center
• Publié dans JAMA oncology le 27/10/2020

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Résumé : Importance: Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1-selected tumors. Objective: To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors. Design, setting, and participants: The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022. Interventions: Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity. Main outcomes and measures: The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables. Results: Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non-small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months). Conclusions and relevance: In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy-naive metastatic NSCLC or EC. Trial registration: ClinicalTrials.gov Identifier: NCT02794571.

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Fichiers liés : Won-Kim_2023.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Sébastien BourdinPhilippe Jean-PierreDavid Perrain
• Organismes : Métis Lab EM Normandie Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion
• Publié dans Eastern Journal of European Studies le 02/11/2020

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Résumé : This article examines the issue of innovation in the tourism sector, emphasising its crucial role in the transformation of the tourist offer within European regions. Faced with territorial disparities in terms of tourism innovations, we examine the impact of Regional Innovation and Smart Specialization Strategies (RIS3) on the deployment of tourism innovation. By analysing the 2014-2020 program through a three-step action research study, we identify a positive correlation between RIS3 initiatives and innovation in the tourism industry. However, RIS3 seem to be a necessary but not sufficient condition to stimulate innovation.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Mélanie CognéArthur DelayrePauline CoignardJean-Luc Le GuietPierre-Alain JosephIsabelle BonanEric SoritaClaire Le GallPhilippe Azouvi
• Organismes : Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Oncostat Hôpital Raymond Poincaré [AP-HP] Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] Centre Mutualiste de Rééducation et de Réadaptation Fonctionnelles de KERPAPE [Ploemeur] Handicap et système nerveux :Action, communication, interaction: rétablissement de la fonction et de la participation [Bordeaux] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Neuroimagerie: méthodes et applications Bordeaux population health Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé - Brest Centre de recherche en épidémiologie et santé des populations
• Publié dans Annals of Physical and Rehabilitation Medicine le 02/11/2020

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Tae Won KimPhilippe BedardPatricia LorussoMichael GordonJohanna BendellDo-Youn OhMyung-Ju AhnElena GarraldaSandra D’angeloJayesh DesaiF. Stephen HodiZev WainbergJean-Pierre DelordPhillippe CassierAndrés CervantesMarta Gil-MartinBenjamin WuNamrata PatilYanling JinTien HoangDiana MendusXiaohui WenRaymond MengByoung Chul Cho
• Organismes : Asan Medical Center [Seoul] Princess Margaret Cancer Center [Toronto] Yale University [New Haven] HonorHealth Research and Innovation Institute, Scottsdale, Arizona. Sarah Cannon Research Institute [Nashville, Tennessee] F. Hoffmann-La Roche [Basel] Seoul National University [Seoul] Samsung Medical Center Sungkyunkwan University School of Medicine Vall d'Hebron University Hospital [Barcelona] Memorial Sloan Kettering Cancer Center Weill Medical College of Cornell University [New York] Peter MacCallum Cancer Centre Dana-Farber Cancer Institute [Boston] Jonsson Comprehensive Cancer Center Institut Universitaire du Cancer de Toulouse - Oncopole Centre Léon Bérard [Lyon] Universitat de València = University of Valencia = Universidade de Valencia Catalan Institute of Oncology [Girona] Genentech, Inc. Genentech, Inc. F. Hoffmann-La Roche A.G. Yonsei University College of Medicine & Medical School, Seoul, Korea
• Publié dans JAMA oncology le 27/10/2020

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Résumé : Importance: Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1-selected tumors. Objective: To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors. Design, setting, and participants: The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022. Interventions: Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity. Main outcomes and measures: The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables. Results: Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non-small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months). Conclusions and relevance: In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy-naive metastatic NSCLC or EC. Trial registration: ClinicalTrials.gov Identifier: NCT02794571.

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Fichiers liés : Kim_2023.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Geoffroy RambaudVicky MaiCamille MotreffOlivier SanchezPierre-Marie RoyYannick AuffretRaphael Le MaoFrédéric GagnadouxNicolas PaleironJeannot SchmidtJean PastreMichel NonentCécile TromeurPierre-Yves SalaunPatrick MismettiPhilippe GirardKarine LacutCatherine LemariéGuy MeyerChristophe LeroyerGrégoire Le GalLaurent BertolettiFrancis Couturaud
• Organismes : Hôpital Morvan - CHRU de Brest Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis U 1059 – SAINBIOSE Bio-ingénierie Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne] U 1059 – SAINBIOSE Bio-ingénierie
• Publié dans Thrombosis Research le 22/10/2020

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