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502 results on '"Cousin S"'

1. Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial

Author

Remon, J., Besse, B., Aix, S. Ponce, Callejo, A., Al-Rabi, K., Bernabe, R., Greillier, L., Majem, M., Reguart, N., Monnet, I., Cousin, S., Garrido, P., Robinet, G., Garcia Campelo, R., Madroszyk, A., Mazières, J., Curcio, H., Wasąg, B., Pretzenbacher, Y., Fournier, B., Dingemans, A.-M.C., and Dziadziuszko, R.

Published
2023
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4. 0.5 keV soft X-ray attosecond continua

Author

Teichmann, S. M., Silva, F., Cousin, S. L., Hemmer, M., and Biegert, J.

Subjects
Physics - Atomic Physics
Abstract

Attosecond light pulses in the extreme ultraviolet have drawn a great deal of attention due to their ability to interrogate electronic dynamics in real time. Nevertheless, to follow charge dynamics and excitations in materials, element selectivity is a prerequisite, which demands such pulses in the soft X-ray region, above 200 eV, to simultaneously cover several fundamental absorption edges of the constituents of the materials. Here, we experimentally demonstrate the exploitation of a transient phase matching regime to generate carrier envelope controlled soft X-ray supercontinua with pulse energies up to 2.9 +/- 0.1 pJ and a flux of (7.3 +/- 0.1)x10^7 photons/s across the entire water window and attosecond pulses with 13 as transform limit. Our results herald attosecond science at the fundamental absorption edges of matter by bridging the gap between ultrafast temporal resolution and element specific probing.

Published
2016
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5. System leadership : are system leaders in the English education system leaders of a profession or instruments of government?

Author

Cousin, S. A.

Subjects
371.2
Abstract

The focus is the activity of 'system leadership' (defined as 'leading beyond a single school'). System Leadership is a feature of the English educational system which is both under-theorised and open to differing interpretations. It is important for three reasons: the proliferation of such roles available to successful headteachers since the concept was introduced in 2003; its high-profile across the terms of New Labour and Coalition Governments; its adaptation by the Conservative Government elected in 2015. The research examines the nature of the concept through the lens of public sector governance in order to more critically examine its characteristics and impact. The reframing of the use of successful leaders from the public service professions as a 'policy steering instrument' has not been considered as part of the literature on governance mechanisms; nor as part of the literature on system leadership, which tends to adopt a normative approach to the concept. The study therefore addresses an important gap in current thinking about the relationship between school leadership and governments' approaches to governance. Insights into the roles come from interviews over the period 2009-2014 with system leaders, headteachers they support and those 'managing' this activity at a mediating or policy level; and analyses of policy documents and performance data. The diachronic view of a high-profile trend over a period of unprecedented radical change in the governance of the English education system offers new understanding of the use of governance instruments and professionals' responses to them. The challenge to adequately conceptualise 'system leadership', heralded for over a decade as the solution to school improvement, was highlighted by Higham, Hopkins and Matthews (2009). The study is therefore timely and important in offering a means of conceptualizing such collaborations, providing individual case studies to illuminate how policy becomes practice in a range of contexts and presenting models of system leadership practice.

Published
2016

7. Caractéristiques et prise en charge des patients porteurs de mutations complexes de l’EGFR dans les cancers bronchiques non à petites cellules : étude multicentrique rétrospective

Author

Atlagh, L., primary, Toublanc, A., additional, Ruuth-Praz, J., additional, Cousin, S., additional, Duruisseaux, M., additional, Chouaid, C., additional, Basset, C., additional, Evrard, S., additional, Girard, N., additional, Mazieres, J., additional, and Brindel, A., additional

Published
2024
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8. Essai randomisé contrôlé comparant l’association pembrolizumab plus chimiothérapie à la chimiothérapie seule dans le mésothéliome pleural avancé, non prétraité (essai IND. 227, IFCT-1901)

Author

Greillier, L., primary, Sanchez, M. Locatelli, additional, Chu, Q., additional, Perrone, F., additional, Zalcman, G., additional, Quantin, X., additional, Mazieres, J., additional, Monnet, I., additional, Madelaine, J., additional, Almotlak, H., additional, Hiret, S., additional, Planchard, D., additional, Molinier, O., additional, Leprieur, E. Giroux, additional, Ricordel, C., additional, Clement-Duchene, C., additional, Cousin, S., additional, Mascaux, C., additional, Audigier-Valette, C., additional, Berndt, C., additional, Seymour, L., additional, Morin, F., additional, Westeel, V., additional, and Scherpereel, A., additional

Published
2024
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10. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors

Author

Italiano, A., Infante, J.R., Shapiro, G.I., Moore, K.N., LoRusso, P.M., Hamilton, E., Cousin, S., Toulmonde, M., Postel-Vinay, S., Tolaney, S., Blackwood, E.M., Mahrus, S., Peale, F.V., Lu, X., Moein, A., Epler, J., DuPree, K., Tagen, M., Murray, E.R., Schutzman, J.L., Lauchle, J.O., Hollebecque, A., and Soria, J.-C.

Published
2018
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13. P2.17-06 Efficacy of Platinum after Lurbinectedin + DOX or Topotecan/CAV in Sensitive Relapsed SCLC Patients in the ATLANTIS Trial

Author

Navarro, A., primary, Smit, E., additional, Carcereny, E., additional, Gutierrez, V., additional, Mavroudis, D., additional, Reinmuth, N., additional, Bustin, F., additional, Lopez-Vilariño, J.A., additional, Gómez, J., additional, Kahatt, C., additional, Zeaiter, A., additional, Cousin, S., additional, Ciuleanu, T.E., additional, Lungulescu, D., additional, Robev, B., additional, and Paz-Ares, L., additional

Published
2023
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15. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial

Author

Aix, S.P. Ciuleanu, T.E. Navarro, A. Cousin, S. Bonanno, L. Smit, E.F. Chiappori, A. Olmedo, M.E. Horvath, I. Grohé, C. Farago, A.F. López-Vilariño, J.A. Cullell-Young, M. Nieto, A. Vasco, N. Gómez, J. Kahatt, C. Zeaiter, A. Carcereny, E. Roubec, J. Syrigos, K. Lo, G. Barneto, I. Pope, A. Sánchez, A. Kattan, J. Zarogoulidis, K. Waller, C.F. Bischoff, H. Juan-Vidal, O. Reinmuth, N. Dómine, M. Paz-Ares, L. and Aix, S.P. Ciuleanu, T.E. Navarro, A. Cousin, S. Bonanno, L. Smit, E.F. Chiappori, A. Olmedo, M.E. Horvath, I. Grohé, C. Farago, A.F. López-Vilariño, J.A. Cullell-Young, M. Nieto, A. Vasco, N. Gómez, J. Kahatt, C. Zeaiter, A. Carcereny, E. Roubec, J. Syrigos, K. Lo, G. Barneto, I. Pope, A. Sánchez, A. Kattan, J. Zarogoulidis, K. Waller, C.F. Bischoff, H. Juan-Vidal, O. Reinmuth, N. Dómine, M. Paz-Ares, L.

Abstract

Background: Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m2 every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC. Methods: In this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/m2 plus doxorubicin 40·0 mg/m2 administered on day 1 of 21-day cycles or physician's choice of control therapy (intravenous topotecan 1·5 mg/m2 on days 1–5 of 21-day cycles; or intravenous cyclophosphamide 1000 mg/m2, doxorubicin 45·0 mg/m2, and vincristine 2·0 mg on day 1 of 21-day cycles [CAV]) administered until disease progression or unacceptable toxicity. Primary granulocyte-colony stimulating factor prophylaxis was mandatory in both treatment groups. Neither patients nor clinicians were masked to treatment allocation, but the independent review committee, which assessed outcomes, was masked to patients' treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02566993, and with EudraCT, 2015-001641-89, and is complete. Findings: Between Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patient

Published
2023

16. Realizing attosecond core-level X-ray spectroscopy for the investigation of condensed matter and for material science

Author

Universitat Politècnica de Catalunya. Doctorat en Fotònica, Summers, A., Severino, Stefano, Reduzzi, Maurizio, Sidiropoulos, Themistoklis P. H., Rivas, Daniel E., Palo, Nicola di, Sun, Hung-wei, Chien, Ying-hao, León, Iker, Buades, Barbara, Cousin, S., Teichmann, Stephan M., Mey, Tobias, Toomey, Tim, Efetov, Dmitri K., Biegert, Jens, Universitat Politècnica de Catalunya. Doctorat en Fotònica, Summers, A., Severino, Stefano, Reduzzi, Maurizio, Sidiropoulos, Themistoklis P. H., Rivas, Daniel E., Palo, Nicola di, Sun, Hung-wei, Chien, Ying-hao, León, Iker, Buades, Barbara, Cousin, S., Teichmann, Stephan M., Mey, Tobias, Toomey, Tim, Efetov, Dmitri K., and Biegert, Jens

Abstract

Unraveling the exact nature of nonequilibrium and correlated interactions is paramount for continued progress in many areas of condensed matter science. Such insight is a prerequisite to develop an engineered approach for smart materials with targeted properties designed to address standing needs such as efficient light harvesting, energy storage, or information processing. For this goal, it is critical to unravel the dynamics of the energy conversion processes between carriers in the earliest time scales of the excitation dynamics. We discuss the implementation and benefits of attosecond soft x-ray core-level spectroscopy up to photon energies of 600 eV for measurements in solid-state systems. In particular, we examine how the pairing between coherent spectral coverage and temporal resolution provides a powerful new insight into the quantum dynamic interactions that determine the macroscopic electronic and optical response. We highlight the different building blocks of the methodology and point out the important aspects for its application from condensed matter studies to materials as thin as 25 nm. Furthermore, we discuss the technological developments in the field of tabletop attosecond soft x-ray sources with time-resolved measurements at the near and extended edge simultaneously and investigate the exciting prospective of extending such technique to the study of 2-dimensional materials., J.B. acknowledges financial support from the European Research Council for ERC Advanced Grant “TRANSFORMER” (788218), ERC Proof of Concept Grant “miniX” (840010), FET-OPEN “PETACom” (829153), FET-OPEN “OPTOlogic” (899794), FET-OPEN “TwistedNano” (101046424), Laserlab-Europe (871124), Marie Skłodowska-Curie ITN “smart-X” (860553), MINECO for Plan Nacional PID2020–112664 GB-I00, AGAUR for 2017 SGR 1639, MINECO for “Severo Ochoa” (CEX2019-000910-S), Fundació Cellex Barcelona, the CERCA Programme/Generalitat de Catalunya, and the Alexander von Humboldt Foundation for the Friedrich Wilhelm Bessel Prize. S.S. acknowledges Marie Skłodowska-Curie grant agreement no. 713729 (COFUND). M.R. and A.M.S. acknowledge Marie Skłodowska-Curie Grant agreement no. 754510 (PROBIST)., Peer Reviewed, Postprint (published version)

Published
2023

17. 10 Osimertinib versus gefitinib followed by osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE trial

Author

Masip, J. Remon, primary, Besse, B., additional, Aix, S. Ponce, additional, Perez, A. Callejo, additional, Al-Rabi, K., additional, Caro, R. Bernabe, additional, Greillier, L., additional, Tarruella, M. Majem, additional, Aransay, N. Reguart, additional, Monnet, I., additional, Cousin, S., additional, Lopez, P. Garrido, additional, Robinet, G., additional, Campelo, R. García, additional, Flandin, A-C. Madroszyk, additional, Mazieres, J., additional, Curcio, H., additional, Pretzenbacher, Y., additional, Dingemans, A-M.C., additional, and Dziadziuszko, R., additional

Published
2023
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19. SMART : étude rétrospective multicentrique des caractéristiques et de la réponse aux traitements des cancers pulmonaire SMARCA4 déficients

Author

Duparc, I., Grecea, M., Castanet, E., Pierret, T., Basse, C., Baldacci, S., Demontrond, P., Morel, H., Fallet, V., Leite-Ferreira, D., Ricordel, C., Arpin, D., Oulkhouir, Y., Bylicki, O., Fournel, P., Roas Ghigna, M., Marinello, A., Bonhomme, B., Besse, B., Aldea, M., Cousin, S., Léturgie, B., Dantoing, E., Roger, M., Salaun, M., Bota, S., Piton, N., and Guisier, F.

Published
2025
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20. Realizing attosecond core-level X-ray spectroscopy for the investigation of condensed matter and for material science

Author

Summers, A., Severino, Stefano, Reduzzi, Maurizio, Sidiropoulos, Themistoklis P. H., Rivas, Daniel E., Palo, Nicola di, Sun, Hung-wei, Chien, Ying-hao, León, Iker, Buades, Barbara, Cousin, S., Teichmann, Stephan M., Mey, Tobias, Toomey, Tim, Efetov, Dmitri K., Biegert, Jens, and Universitat Politècnica de Catalunya. Doctorat en Fotònica

Subjects
Anàlisi espectral, Electromagnetism, Física::Electromagnetisme [Àrees temàtiques de la UPC], Electromagnetisme, Spectrum analysis
Abstract

Unraveling the exact nature of nonequilibrium and correlated interactions is paramount for continued progress in many areas of condensed matter science. Such insight is a prerequisite to develop an engineered approach for smart materials with targeted properties designed to address standing needs such as efficient light harvesting, energy storage, or information processing. For this goal, it is critical to unravel the dynamics of the energy conversion processes between carriers in the earliest time scales of the excitation dynamics. We discuss the implementation and benefits of attosecond soft x-ray core-level spectroscopy up to photon energies of 600 eV for measurements in solid-state systems. In particular, we examine how the pairing between coherent spectral coverage and temporal resolution provides a powerful new insight into the quantum dynamic interactions that determine the macroscopic electronic and optical response. We highlight the different building blocks of the methodology and point out the important aspects for its application from condensed matter studies to materials as thin as 25 nm. Furthermore, we discuss the technological developments in the field of tabletop attosecond soft x-ray sources with time-resolved measurements at the near and extended edge simultaneously and investigate the exciting prospective of extending such technique to the study of 2-dimensional materials. J.B. acknowledges financial support from the European Research Council for ERC Advanced Grant “TRANSFORMER” (788218), ERC Proof of Concept Grant “miniX” (840010), FET-OPEN “PETACom” (829153), FET-OPEN “OPTOlogic” (899794), FET-OPEN “TwistedNano” (101046424), Laserlab-Europe (871124), Marie Skłodowska-Curie ITN “smart-X” (860553), MINECO for Plan Nacional PID2020–112664 GB-I00, AGAUR for 2017 SGR 1639, MINECO for “Severo Ochoa” (CEX2019-000910-S), Fundació Cellex Barcelona, the CERCA Programme/Generalitat de Catalunya, and the Alexander von Humboldt Foundation for the Friedrich Wilhelm Bessel Prize. S.S. acknowledges Marie Skłodowska-Curie grant agreement no. 713729 (COFUND). M.R. and A.M.S. acknowledge Marie Skłodowska-Curie Grant agreement no. 754510 (PROBIST).

Published
2023

21. Molecular characterization of primary and secondary resistance to RET inhibitors in patients with advanced NSCLC and RET fusions

Author

Marinello, A., primary, Vasseur, D., additional, Conci, N., additional, Lindsay, C., additional, Metro, G., additional, Ferrara, R., additional, Eisert, A., additional, Citarella, F., additional, Fallet, V., additional, Audugier-Valette, C., additional, Cousin, S., additional, Tabbò, F., additional, Russo, A., additional, Calles Blanco, A., additional, Iranzo Gomez, P., additional, Tagliamento, M., additional, Mezquita, L., additional, Ponce, S., additional, Besse, B., additional, and Aldea, M., additional

Published
2022
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23. LBA51 Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial

Author

Masip, J. Remon, primary, Besse, B., additional, Aix, S. Ponce, additional, Callejo, A., additional, Al-Rabi, K., additional, Caro, R. Bernabe, additional, Greillier, L., additional, Tarruella, M. Majem, additional, Aransay, N. Reguart, additional, Monnet, I., additional, Cousin, S., additional, Lopez, P. Garrido, additional, Robinet, G., additional, Campelo, M.R. Garcia, additional, Flandin, A-C. Madroszyk, additional, Mazieres, J., additional, Pretzenbacher, Y., additional, Fournier, B., additional, Dingemans, A-M.C., additional, and Dziadziuszko, R., additional

Published
2022
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24. 1189TiP Phase II study of anti-TIGIT GSK4428859A (GSK’859A)/EOS-448 + anti-CD96 GSK6097608 (GSK’608) + anti-PD-1 dostarlimab in non-small cell lung cancer (NSCLC)

Author

Spigel, D.R., primary, Garrido Lopez, P., additional, Cousin, S., additional, Cheema, P.K., additional, Rodríguez, L.M., additional, Garassino, M.C., additional, Kijewska, M., additional, Majumdar, A., additional, Theti, D.S., additional, Roy-Ghanta, S., additional, Ballas, M., additional, and Reck, M., additional

Published
2022
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25. 1742P Phase II study of rucaparib and atezolizumab (ARIANES): Results in patients (pts) with platinum-sensitive metastatic urothelial cancer (mUC) and metastatic castration-resistant prostate cancer (mCRPC)

Author

Martin Romano, P., primary, Roubaud, G., additional, Lavaud, P., additional, Cabart, M., additional, Pages, A., additional, Vasseur, D., additional, Colomba, E., additional, Cousin, S., additional, Toulmonde, M., additional, Grellety, T., additional, Castel Ajgal, Z., additional, Chabanon, R., additional, Parpaleix, A., additional, Buzzatti, G., additional, Fizazi, K., additional, Gomez-Roca, C.A., additional, Italiano, A., additional, Loriot, Y., additional, and Postel-Vinay, S., additional

Published
2022
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26. 1525TiP TORNADO: A randomized multicenter open-label phase II study evaluating retifanlimab in combination with neoadjuvant chemotherapy in patients with selected retroperitoneal sarcomas

Author

Albert, S., primary, Italiano, A., additional, Toulmonde, M., additional, Cousin, S., additional, Bahleda, R., additional, Brahmi, M., additional, Watson, S., additional, Auzanneau, C., additional, Douiri, N., additional, Poignie, L., additional, Lortal, B., additional, Le Loarer, F., additional, and Bellera, C., additional

Published
2022
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27. 1007P Mechanisms of primary and secondary resistance to RET inhibitors in patients with RET-positive advanced NSCLC

Author

Marinello, A., primary, Vasseur, D., additional, Conci, N., additional, Fallet, V., additional, Audigier-Valette, C., additional, Cousin, S., additional, Tabbò, F., additional, Guisier, F., additional, Russo, A., additional, Calles Blanco, A., additional, Metro, G., additional, Massa, G., additional, Citarella, F., additional, Eisert, A.K., additional, Iranzo Gomez, P., additional, Tagliamento, M., additional, Mezquita, L., additional, Lindsay, C., additional, Ponce, S., additional, and Aldea, M., additional

Published
2022
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28. 1640TiP PECATI: A phase II trial to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab in pretreated advanced b3-thymoma (B3-T) and thymic carcinoma (TC)

Author

Remon Masip, J., primary, Girard, N., additional, Bironzo, P., additional, Novello, S., additional, De Castro Carpeno, J., additional, Bigay-Game, L., additional, Bernabe Caro, R., additional, Greillier, L., additional, Mosquera Martinez, J., additional, Cousin, S., additional, Juan Vidal, O.J., additional, Sampayo-Cordero, M., additional, and Besse, B., additional

Published
2022
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29. 1527TiP CONGRATS-combination of nivolumab plus relatlimab in patients with advanced or metastatic soft-tissue sarcoma: A proof-of-concept randomized phase II study

Author

Spalato Ceruso, M., primary, Albert, S., additional, Italiano, A., additional, Toulmonde, M., additional, Cousin, S., additional, Grellety, T., additional, Blay, J-Y., additional, Verret, B., additional, Auzanneau, C., additional, Valade, V., additional, Poignie, L., additional, Lortal, B., additional, Kind, M., additional, Le Loarer, F., additional, and Pulido, M., additional

Published
2022
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31. 781TiP AGADIR: A basket multicenter open-label phase II study evaluating the first in class TLR7/8 agonist BDB001 in combination with atezolizumab and stereotactic body radiation therapy in patients with advanced solid tumors

Author

Italiano, A., primary, Coutzac Bergouignan, C., additional, Pasquier, D., additional, Rochigneux, P., additional, Sablin, M.P., additional, Gomez-Roca, C.A., additional, Ghiringhelli, F., additional, Metges, J-P., additional, Toulmonde, M., additional, Cousin, S., additional, Pernot, S., additional, Auzanneau, C., additional, Lortal, B., additional, Kind, M., additional, Sargos, P., additional, Batard, S., additional, Petit, A., additional, Gillon, P., additional, Albert, S., additional, and Pulido, M., additional

Published
2022
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35. LBA83 PECATI: A phase II trial to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab in pretreated advanced B3-thymoma and thymic carcinoma

Author

Remon Masip, J., Bironzo, P., Girard, N., Bigay-Game, L., Juan Vidal, O.J., de Castro Carpeño, J., Reguart Aransay, N., Greillier, L., Cousin, S., Dansin, E., Majem, M., Bernabe Caro, R., Mosquera Martinez, J., Diaz, M., Meya, A., Alcalá-López, D., Sanz, A.G., Righi, L., Novello, S., and Besse, B.

Published
2024
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39. 1259MO Encorafenib plus binimetinib in patients (pts) with previously untreated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC): An open-label, multicenter phase II trial (IFCT-1904 ENCO-BRAF)

Author

Planchard, D., Mazieres, J., Mascaux, C., Guisier, F., Tomasini, P., Wislez, M., Moro-Sibilot, D., Cousin, S., Cortot, A.B., Couraud, S., Fallet, V., Guguen, C., Lagrange, A., Madroszyk Flandin, A-C., Otto, J., Pérol, M., Roch, B., Amour, E., Morin, F., and Ricordel, C.

Published
2024
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46. Étude rétrospective de la mise en place du certificat de compétences cliniques (C3) au format ECOS (examen clinique objectif structuré) au sein d’une faculté de médecine française

Author

Machouche, S., primary, Debien, B., additional, Mattatia, L., additional, Carbonnel, F., additional, Dupeyron, A., additional, Claret, P.G., additional, Thieblemont, T., additional, Cousin, S., additional, Capdevielle, D., additional, Morin, D., additional, Mondain, M., additional, Laffont, I., additional, and Guilpain, P., additional

Published
2022
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47. Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein of the testis carcinoma and other cancers: Results of a Phase I/II open-label, dose escalation study

Author

Cousin, S, Blay, J-Y, Garcia, IB, de Bono, JS, Le Tourneau, C, Moreno, V, Trigo, J, Hann, CL, Azad, AA, Im, S-A, Cassier, PA, French, CA, Italiano, A, Keedy, VL, Plummer, R, Sablin, M-P, Hemming, ML, Ferron-Brady, G, Wyce, A, Khaled, A, Datta, A, Foley, SW, McCabe, MT, Wu, Y, Horner, T, Kremer, BE, Dhar, A, O'Dwyer, PJ, Shapiro, GI, Piha-Paul, SA, Cousin, S, Blay, J-Y, Garcia, IB, de Bono, JS, Le Tourneau, C, Moreno, V, Trigo, J, Hann, CL, Azad, AA, Im, S-A, Cassier, PA, French, CA, Italiano, A, Keedy, VL, Plummer, R, Sablin, M-P, Hemming, ML, Ferron-Brady, G, Wyce, A, Khaled, A, Datta, A, Foley, SW, McCabe, MT, Wu, Y, Horner, T, Kremer, BE, Dhar, A, O'Dwyer, PJ, Shapiro, GI, and Piha-Paul, SA

Abstract

Molibresib is an orally bioavailable, selective, small molecule BET protein inhibitor. Results from a first time in human study in solid tumors resulted in the selection of a 75 mg once daily dose of the besylate formulation of molibresib as the recommended Phase 2 dose (RP2D). Here we present the results of Part 2 of our study, investigating safety, pharmacokinetics, pharmacodynamics and clinical activity of molibresib at the RP2D for nuclear protein in testis carcinoma (NC), small cell lung cancer, castration-resistant prostate cancer (CRPC), triple-negative breast cancer, estrogen receptor-positive breast cancer and gastrointestinal stromal tumor. The primary safety endpoints were incidence of adverse events (AEs) and serious AEs; the primary efficacy endpoint was overall response rate. Secondary endpoints included plasma concentrations and gene set enrichment analysis (GSEA). Molibresib 75 mg once daily demonstrated no unexpected toxicities. The most common treatment-related AEs (any grade) were thrombocytopenia (64%), nausea (43%) and decreased appetite (37%); 83% of patients required dose interruptions and 29% required dose reductions due to AEs. Antitumor activity was observed in NC and CRPC (one confirmed partial response each, with observed reductions in tumor size), although predefined clinically meaningful response rates were not met for any tumor type. Total active moiety median plasma concentrations after single and repeated administration were similar across tumor cohorts. GSEA revealed that gene expression changes with molibresib varied by patient, response status and tumor type. Investigations into combinatorial approaches that use BET inhibition to eliminate resistance to other targeted therapies are warranted.

Published
2022

48. Mechanisms of primary and secondary resistance to RET inhibitors in patients with RET-positive advanced NSCLC

Author

Marinello, A., Vasseur, D., Conci, N., Fallet, V., Audigier-Valette, C., Cousin, S., Tabbo, F., Guisier, F., Russo, A., Blanco, A. Calles, Metro, G., Massa, G., Citarella, F., Eisert, A. K., Gomez, P. Iranzo, Tagliamento, M., Mezquita, L., Lindsay, C., Ponce, S., Aldea, M., Marinello, A., Vasseur, D., Conci, N., Fallet, V., Audigier-Valette, C., Cousin, S., Tabbo, F., Guisier, F., Russo, A., Blanco, A. Calles, Metro, G., Massa, G., Citarella, F., Eisert, A. K., Gomez, P. Iranzo, Tagliamento, M., Mezquita, L., Lindsay, C., Ponce, S., and Aldea, M.

Published
2022

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