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2. A Phase 1a/1b Study of Fostroxacitabine Bralpamide (Fostrox) Monotherapy in Hepatocellular Carcinoma and Solid Tumor Liver Metastases

Author

Plummer R, Greystoke A, Naylor G, Sarker D, Anam ANMK, Prenen H, Teuwen LA, Van Cutsem E, Dekervel J, Haugk B, Ness T, Bhoi S, Jensen M, Morris T, Baumann P, Sjögren N, Tunblad K, Wallberg H, Öberg F, and Evans TRJ

Subjects
phase 1, fostrox, hepatocellular carcinoma, nucleotide prodrug, pharmacokinetics, pharmacodynamics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Ruth Plummer,1 Alastair Greystoke,1 Gregory Naylor,2 Debashis Sarker,3,4 ANM Kaiser Anam,4 Hans Prenen,5 Laure-Anne Teuwen,5 Eric Van Cutsem,6 Jeroen Dekervel,6 Beate Haugk,1 Thomas Ness,1 Sujata Bhoi,7 Malene Jensen,7 Tom Morris,7 Pia Baumann,7 Niclas Sjögren,8 Karin Tunblad,7 Hans Wallberg,7 Fredrik Öberg,7 Thomas R Jeffry Evans2 1Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 2Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK; 3School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK; 4Department of Medical Oncology, Guy’s Hospital, London, UK; 5Department of Oncology, Antwerp University Hospital, Edegem, Belgium; 6Department of Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium; 7Medivir AB, Huddinge, Sweden; 8SDS Life Science, Stockholm, SwedenCorrespondence: Pia Baumann, Medivir AB, Box 1086, SE-141 22, Huddinge, Sweden, Tel +46 739163897, Email pia.baumann@medivir.comPurpose: To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.Patients and Methods: Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.Results: Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.Conclusion: The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.Keywords: phase 1, fostrox, hepatocellular carcinoma, nucleotide prodrug, pharmacokinetics, pharmacodynamics

Published
2024

9. Large sulfur isotope fractionations in Martian sediments at Gale crater

Author

Franz, HB, McAdam, AC, Ming, DW, Freissinet, C, Mahaffy, PR, Eldridge, DL, Fischer, WW, Grotzinger, JP, House, CH, Hurowitz, JA, McLennan, SM, Schwenzer, SP, Vaniman, DT, Archer Jr, PD, Atreya, SK, Conrad, PG, Dottin III, JW, Eigenbrode, JL, Farley, KA, Glavin, DP, Johnson, SS, Knudson, CA, Morris, RV, Navarro-González, R, Pavlov, AA, Plummer, R, Rampe, EB, Stern, JC, Steele, A, Summons, RE, and Sutter, B

Subjects
Meteorology & Atmospheric Sciences
Abstract

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA's Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of Δ34S range from - 47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods.

Published
2017

10. Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study

Author

Pant, S, Schuler, M, Iyer, G, Witt, O, Doi, T, Qin, S, Tabernero, J, Reardon, D, Massard, C, Minchom, A, Lugowska, I, Carranza, O, Arnold, D, Gutierrez, M, Winter, H, Stuyckens, K, Crow, L, Najmi, S, Hammond, C, Thomas, S, Santiago-Walker, A, Triantos, S, Sweiti, H, Loriot, Y, Greco, M, Coward, J, Joshua, A, Karapetis, C, Hart, C, Zhang, A, Prenen, H, Goeminne, J, Machiels, J, Rottey, S, Corassa, M, Molin, G, Tiscoski, K, Jardim, D, Mak, M, Fu, W, Yao, H, Huang, J, Jiang, H, Chen, B, Yan, D, Yang, Y, Le Tourneau, C, Penel, N, Salas, S, Blay, J, Brachet, P, Durando, X, Emambux, S, Ravaud, A, Folprecht, G, Ahrens, M, Golf, A, Haag, G, Lordick, F, Desuki, A, Cazzaniga, M, Ciardiello, F, Milella, M, Koyama, T, Hirooka, Y, Okamoto, W, Aogi, K, Kuboki, Y, Lee, J, Kim, S, Ahn, M, Chang, J, Kim, Y, Nam, D, Park, J, Paz-Ares, L, Moreno, V, Cervantes, A, Calvo, M, Falcon, A, Gonzalez, A, Martinez Bueno, A, Garcia-Corbacho, J, Longo, F, Yen, C, Chen, J, Hou, M, Chao, Y, Rau, K, Chiu, T, Feng, Y, Hsu, C, Huang, W, Lai, K, Yeh, S, Palmer, D, Welsh, L, Plummer, R, Bilen, M, Arrowsmith, E, Spigel, D, Zandberg, D, Doroshow, D, Lu-Emerson, C, Moezi, M, Paulson, S, Ward, P, Chaves, J, Grigg, C, Hussein, A, Manda, S, Monticelli, M, Qamar, R, Richey, S, Tamura, D, Wilks, S, Pant S., Schuler M., Iyer G., Witt O., Doi T., Qin S., Tabernero J., Reardon D. A., Massard C., Minchom A., Lugowska I., Carranza O., Arnold D., Gutierrez M., Winter H., Stuyckens K., Crow L., Najmi S., Hammond C., Thomas S., Santiago-Walker A., Triantos S., Sweiti H., Loriot Y., Greco M. A., Coward J., Joshua A., Karapetis C., Hart C., Zhang A., Prenen H., Goeminne J. -C., Machiels J. -P., Rottey S., Corassa M., Molin G. Z. D., Tiscoski K., Jardim D. L. F., Mak M., Fu W., Yao H., Huang J., Jiang H., Chen B., Yan D., Yang Y., Le Tourneau C., Penel N., Salas S., Blay J. -Y., Brachet P. -E., Durando X., Emambux S., Ravaud A., Folprecht G., Ahrens M., Golf A., Haag G. M., Lordick F., Desuki A., Cazzaniga M., Ciardiello F., Milella M., Koyama T., Hirooka Y., Okamoto W., Aogi K., Kuboki Y., Lee J., Kim S. -B., Ahn M. -J., Chang J. H., Kim Y. -M., Nam D. -H., Park J. -S., Paz-Ares L., Moreno V., Cervantes A., Calvo M., Falcon A., Gonzalez A., Martinez Bueno A., Garcia-Corbacho J., Longo F., Yen C. -J., Chen J. -S., Hou M. -F., Chao Y., Rau K. -M., Chiu T. -J., Feng Y. -H., Hsu C. -H., Huang W. -T., Lai K. -M., Yeh S. -P., Palmer D., Welsh L., Plummer R., Bilen M., Arrowsmith E., Spigel D. R., Zandberg D. P., Doroshow D., Lu-Emerson C., Moezi M., Paulson S., Reardon D., Ward P., Chaves J., Grigg C., Hussein A., Manda S., Monticelli M., Qamar R., Richey S. L., Tamura D., Wilks S., Pant, S, Schuler, M, Iyer, G, Witt, O, Doi, T, Qin, S, Tabernero, J, Reardon, D, Massard, C, Minchom, A, Lugowska, I, Carranza, O, Arnold, D, Gutierrez, M, Winter, H, Stuyckens, K, Crow, L, Najmi, S, Hammond, C, Thomas, S, Santiago-Walker, A, Triantos, S, Sweiti, H, Loriot, Y, Greco, M, Coward, J, Joshua, A, Karapetis, C, Hart, C, Zhang, A, Prenen, H, Goeminne, J, Machiels, J, Rottey, S, Corassa, M, Molin, G, Tiscoski, K, Jardim, D, Mak, M, Fu, W, Yao, H, Huang, J, Jiang, H, Chen, B, Yan, D, Yang, Y, Le Tourneau, C, Penel, N, Salas, S, Blay, J, Brachet, P, Durando, X, Emambux, S, Ravaud, A, Folprecht, G, Ahrens, M, Golf, A, Haag, G, Lordick, F, Desuki, A, Cazzaniga, M, Ciardiello, F, Milella, M, Koyama, T, Hirooka, Y, Okamoto, W, Aogi, K, Kuboki, Y, Lee, J, Kim, S, Ahn, M, Chang, J, Kim, Y, Nam, D, Park, J, Paz-Ares, L, Moreno, V, Cervantes, A, Calvo, M, Falcon, A, Gonzalez, A, Martinez Bueno, A, Garcia-Corbacho, J, Longo, F, Yen, C, Chen, J, Hou, M, Chao, Y, Rau, K, Chiu, T, Feng, Y, Hsu, C, Huang, W, Lai, K, Yeh, S, Palmer, D, Welsh, L, Plummer, R, Bilen, M, Arrowsmith, E, Spigel, D, Zandberg, D, Doroshow, D, Lu-Emerson, C, Moezi, M, Paulson, S, Ward, P, Chaves, J, Grigg, C, Hussein, A, Manda, S, Monticelli, M, Qamar, R, Richey, S, Tamura, D, Wilks, S, Pant S., Schuler M., Iyer G., Witt O., Doi T., Qin S., Tabernero J., Reardon D. A., Massard C., Minchom A., Lugowska I., Carranza O., Arnold D., Gutierrez M., Winter H., Stuyckens K., Crow L., Najmi S., Hammond C., Thomas S., Santiago-Walker A., Triantos S., Sweiti H., Loriot Y., Greco M. A., Coward J., Joshua A., Karapetis C., Hart C., Zhang A., Prenen H., Goeminne J. -C., Machiels J. -P., Rottey S., Corassa M., Molin G. Z. D., Tiscoski K., Jardim D. L. F., Mak M., Fu W., Yao H., Huang J., Jiang H., Chen B., Yan D., Yang Y., Le Tourneau C., Penel N., Salas S., Blay J. -Y., Brachet P. -E., Durando X., Emambux S., Ravaud A., Folprecht G., Ahrens M., Golf A., Haag G. M., Lordick F., Desuki A., Cazzaniga M., Ciardiello F., Milella M., Koyama T., Hirooka Y., Okamoto W., Aogi K., Kuboki Y., Lee J., Kim S. -B., Ahn M. -J., Chang J. H., Kim Y. -M., Nam D. -H., Park J. -S., Paz-Ares L., Moreno V., Cervantes A., Calvo M., Falcon A., Gonzalez A., Martinez Bueno A., Garcia-Corbacho J., Longo F., Yen C. -J., Chen J. -S., Hou M. -F., Chao Y., Rau K. -M., Chiu T. -J., Feng Y. -H., Hsu C. -H., Huang W. -T., Lai K. -M., Yeh S. -P., Palmer D., Welsh L., Plummer R., Bilen M., Arrowsmith E., Spigel D. R., Zandberg D. P., Doroshow D., Lu-Emerson C., Moezi M., Paulson S., Reardon D., Ward P., Chaves J., Grigg C., Hussein A., Manda S., Monticelli M., Qamar R., Richey S. L., Tamura D., and Wilks S.

Abstract

Background: FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours. Methods: The single-arm, phase 2 RAGNAR study was conducted at 156 investigative centres (hospitals or oncology practices that are qualified oncology study centres) across 15 countries. The study consisted of four cohorts based on tumour histology and patient age; the results reported in this Article are for the primary cohort of the study, defined as the Broad Panel Cohort, which was histology-agnostic. We recruited patients aged 12 years or older with advanced or metastatic tumours of any histology (except urothelial cancer) with predefined FGFR1–4 alterations (mutations or fusions according to local or central testing). Eligible patients had disease progression on at least one previous line of systemic therapy and no alternative standard therapy available to them, and an Eastern Cooperative Oncology Group performance status of 0–1 (or equivalent for adolescents aged 12–17 years). Patients received once-daily oral erdafitinib (8 mg/day with provision for pharmacodynamically guided up-titration to 9 mg/day) on a continuous 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate by independent review committee according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, or Response Assessment In Neuro-Oncology (RANO). The primary analysis was conducted on the treated population of the Broad Panel Cohort. This ongoing study is registered with ClinicalTrials.gov, number NCT04083976. Findings: Patients were recruited between Dec 5, 2019, and Feb 15, 2022. Of 217 patients treated with erdafitinib, 97 (45%) pa

Published
2023

11. 80P Social determinants of health inequalities in early phase clinical trials in Northern England

Author

Rae, S.C.A., primary, Shaya, S.J., additional, Taylor, E., additional, Hoben, J., additional, Oluwashegun, D., additional, Lowe, H., additional, Haris, N.R., additional, Bashir, S., additional, Oing, C., additional, Krebs, M.G., additional, Thistlethwaite, F., additional, Carter, L., additional, Cook, N., additional, Greystoke, A., additional, Graham, D.M., additional, and Plummer, R., additional

Published
2024
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12. 134P A phase I study exploring the safety and tolerability of the small molecule PD-L1 inhibitor INCB099318 in select advanced solid tumors

Author

Pinato, D.J., primary, Banerji, U., additional, Rottey, S., additional, Peltola, K., additional, Yachnin, J., additional, Kristeleit, R., additional, Gutierrez, M., additional, Symeonides, S.N., additional, Jebsen, N.L., additional, Hoejgaard, M., additional, Edenfield, W., additional, Smeland, K.B., additional, Schiza, A., additional, Ny, L., additional, Ebiana, V., additional, Daniel, J., additional, Pulini, J., additional, and Plummer, R., additional

Published
2023
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14. Design and conduct of early clinical studies of immunotherapy agent combinations: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies

Author

Atkins, M., Banerji, U., Bates, S., Bogaerts, J., Calvo, E., De Braud, F., Douillard, J.Y., Giaccone, G., Keegan, P., Kumar, R., LoRusso, P., Marabelle, A., Perrone, A., Pignatti, F., Plummer, R., Seymour, L., Schwartz, G., Shalabi, A., Shapiro, G., Siu, L.L., Smoragiewicz, M., Tabernero, J., Therasse, P., and Yang, A.

Published
2018
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15. A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors

Author

Soria, J.C., Gan, H.K., Blagden, S.P., Plummer, R., Arkenau, H.T., Ranson, M., Evans, T.R.J., Zalcman, G., Bahleda, R., Hollebecque, A., Lemech, C., Dean, E., Brown, J., Gibson, D., Peddareddigari, V., Murray, S., Nebot, N., Mazumdar, J., Swartz, L., Auger, K.R., Fleming, R.A., Singh, R., and Millward, M.

Published
2016
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16. First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers

Author

Felip, E, Moreno, V, Morgensztern, D, Curigliano, G, Rutkowski, P, Trigo, J, Calvo, A, Kowalski, D, Cortinovis, D, Plummer, R, Maio, M, Ascierto, P, Vladimirov, V, Cervantes, A, Zudaire, E, Hazra, A, T'Jollyn, H, Bandyopadhyay, N, Greger, J, Attiyeh, E, Xie, H, Calvo, E, Felip E, Moreno V, Morgensztern D, Curigliano G, Rutkowski P, Trigo JM, Calvo A, Kowalski D, Cortinovis D, Plummer R, Maio M, Ascierto PA, Vladimirov VI, Cervantes A, Zudaire E, Hazra A, T'jollyn H, Bandyopadhyay N, Greger JG, Attiyeh E, Xie H, Calvo E, Felip, E, Moreno, V, Morgensztern, D, Curigliano, G, Rutkowski, P, Trigo, J, Calvo, A, Kowalski, D, Cortinovis, D, Plummer, R, Maio, M, Ascierto, P, Vladimirov, V, Cervantes, A, Zudaire, E, Hazra, A, T'Jollyn, H, Bandyopadhyay, N, Greger, J, Attiyeh, E, Xie, H, Calvo, E, Felip E, Moreno V, Morgensztern D, Curigliano G, Rutkowski P, Trigo JM, Calvo A, Kowalski D, Cortinovis D, Plummer R, Maio M, Ascierto PA, Vladimirov VI, Cervantes A, Zudaire E, Hazra A, T'jollyn H, Bandyopadhyay N, Greger JG, Attiyeh E, Xie H, and Calvo E

Abstract

Purpose: To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study. Methods: In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability–high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter. Results: In phase 1, 58 patients received cetrelimab. Two dose-limiting toxicities were reported and two recommended phase 2 doses (RP2D) were defined (240 mg Q2W or 480 mg Q4W). After a first dose, mean maximum serum concentrations (Cmax) ranged from 24.7 to 227.0 µg/mL; median time to Cmax ranged from 2.0 to 3.2 h. Pharmacodynamic effect was maintained throughout the dosing period across doses. In phase 2, 146 patients received cetrelimab 240 mg Q2W. Grade ≥ 3 adverse events (AEs) occurred in 53.9% of patients. Immune-related AEs (any grade) occurred in 35.3% of patients (grade ≥ 3 in 6.9%). Overall response rate was 18.6% across tumor types, 34.3% in NSCLC, 52.6% in programmed death ligand 1–high (≥ 50% by immunohistochemistry) NSCLC, 28.0% in melanoma, and 23.8% in centrally confirmed MSI-H CRC. Conclusions: The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors. Trial registrations: NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016–002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.

Published
2022

17. Off-label, but on target: the evidence needed to implement alternative dosing regimens of anticancer drugs.

Author

Overbeek, J.K., Heine, R. ter, Verheul, H.M.W., Chatelut, E., Rudek, M.A., Gurney, H., Plummer, R., Gilbert, D.C., Buclin, T., Burger, D.M., Bloemendal, H.J., Erp, N.P. van, Overbeek, J.K., Heine, R. ter, Verheul, H.M.W., Chatelut, E., Rudek, M.A., Gurney, H., Plummer, R., Gilbert, D.C., Buclin, T., Burger, D.M., Bloemendal, H.J., and Erp, N.P. van

Abstract

01 februari 2023, Item does not contain fulltext

Published
2023

18. Collaboration and individual performance during disaster response

Author

Guerrero, A. M., Bodin, O., Nohrstedt, Daniel, Plummer, R., Baird, J., Summers, R., Guerrero, A. M., Bodin, O., Nohrstedt, Daniel, Plummer, R., Baird, J., and Summers, R.

Abstract

Disasters occurring in the wake of extreme weather events are increasing in frequency and severity due to climate and anthropogenic changes and require urgent responses under uncertain and dynamic conditions. In these situations, multi-agency collaboration becomes integral to an effective response due to the need to coordinate actions across geographical scales, levels of authority and sectors of society. Consequently there is a need for more knowledge on how to enhance the effectiveness of collaborations in response to disasters. In this study we utilize extremely rare and comprehensive data on multi-stakeholder collaboration during the acute phase of two catastrophic wildfires to investigate performance in relation to four collaboration challenges: sharing information, conflict resolution, reaching agreement i.e. mutual understanding and commitment, on goals and workingmethods, and coordinating activities. Our results suggest that agreement between collaborating actors is more important to individual performance than the coordination of activities, and that it is only when agreement exists that the ability to coordinate activities becomes highly important. This study allows, for the first time, insights into the detailed nuances of collaboration among individuals during rapidly evolving disaster situations. Importantly, our analysis suggests that focusing on enhancing agreement in the wake of disasters-and not only on improving coordination-could reduce the devastating effects that disasters have on people and ecosystems.

Published
2023
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20. 83P Evaluation of response-predictive biomarkers for lisavanbulin: A phase II study in patients with recurrent glioblastoma

Author

Lopez, J.S., primary, Häfliger, S., additional, Plummer, R., additional, Clement, P.M., additional, Läubli, H., additional, Roth, P., additional, Evans, T., additional, Brazil, L., additional, Tabatabai, G., additional, Wick, A., additional, Wing, Y., additional, Wunderlich, B., additional, Beebe, K.D., additional, Eisner, J., additional, Engelhardt, M., additional, Kaindl, T., additional, Lane, H.A., additional, Hau, P., additional, Hundsberger, T., additional, and Steinbach, J., additional

Published
2023
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31. Staging and prognostic factors

Author

Ascierto, P A, Lugowska, I, Plummer, R, Ascierto, P A ( P A ), Lugowska, I ( I ), Plummer, R ( R ), Ramelyte, E; https://orcid.org/0000-0001-8262-8608, Dummer, R; https://orcid.org/0000-0002-2279-6906, Ascierto, P A, Lugowska, I, Plummer, R, Ascierto, P A ( P A ), Lugowska, I ( I ), Plummer, R ( R ), Ramelyte, E; https://orcid.org/0000-0001-8262-8608, and Dummer, R; https://orcid.org/0000-0002-2279-6906

Published
2021

34. 529MO Phase II study of olaparib plus durvalumab with or without bevacizumab (MEDIOLA): Final analysis of overall survival in patients with non-germline BRCA-mutated platinum-sensitive relapsed ovarian cancer

Author

Banerjee, S., primary, Imbimbo, M., additional, Roxburgh, P., additional, Kim, J-W., additional, Kim, M.H., additional, Plummer, R., additional, Stemmer, S., additional, You, B., additional, Ferguson, M., additional, Penson, R.T., additional, O'Malley, D., additional, Meyer, K., additional, Gao, H., additional, Angell, H., additional, Tablante Nunes, A., additional, Domchek, S., additional, and Drew, Y., additional

Published
2022
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42. PB2099: A FIRST-IN-HUMAN PHASE 1 TRIAL OF NX-1607, A FIRST-IN-CLASS ORAL CBL-B INHIBITOR, IN PATIENTS WITH ADVANCED MALIGNANCIES INCLUDING RICHTER TRANSFORMATION DLBCL

Author

Sharp, A., primary, Williams, A., additional, Blagden, S., additional, Plummer, R., additional, Hochhauser, D., additional, Krebs, M. G., additional, Pacey, S., additional, Evans, J., additional, Whelan, S., additional, Nandakumar, S., additional, Rogers, S., additional, Jameson, K. L., additional, Basile, F. G., additional, de Bono, J., additional, and Arkenau, H.-T., additional

Published
2022
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43. 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

44. Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma

Author

Bhave, P, Ahmed, T, Lo, SN, Shoushtari, A, Zaremba, A, Versluis, JM, Mangana, J, Weichenthal, M, Si, L, Lesimple, T, Robert, C, Trojanello, C, Wicky, A, Heywood, R, Tran, L, Batty, K, Dimitriou, F, Stansfeld, A, Allayous, C, Schwarze, JK, Mooradian, MJ, Klein, O, Mehmi, I, Roberts-Thomson, R, Maurichi, A, Yeoh, H-L, Khattak, A, Zimmer, L, Blank, CU, Ramelyte, E, Kaehler, KC, Roy, S, Ascierto, PA, Michielin, O, Lorigan, PC, Johnson, DB, Plummer, R, Lebbe, C, Neyns, B, Sullivan, R, Hamid, O, Santinami, M, McArthur, GA, Haydon, AM, Long, G, Menzies, AM, Carlino, MS, Bhave, P, Ahmed, T, Lo, SN, Shoushtari, A, Zaremba, A, Versluis, JM, Mangana, J, Weichenthal, M, Si, L, Lesimple, T, Robert, C, Trojanello, C, Wicky, A, Heywood, R, Tran, L, Batty, K, Dimitriou, F, Stansfeld, A, Allayous, C, Schwarze, JK, Mooradian, MJ, Klein, O, Mehmi, I, Roberts-Thomson, R, Maurichi, A, Yeoh, H-L, Khattak, A, Zimmer, L, Blank, CU, Ramelyte, E, Kaehler, KC, Roy, S, Ascierto, PA, Michielin, O, Lorigan, PC, Johnson, DB, Plummer, R, Lebbe, C, Neyns, B, Sullivan, R, Hamid, O, Santinami, M, McArthur, GA, Haydon, AM, Long, G, Menzies, AM, and Carlino, MS

Abstract

BACKGROUND: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site. METHODS: Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites. CONCLUSION: While the ORR to anti-PD-1/ipilimumab wa

Published
2022

46. 8P Pharmacokinetic (PK) profile and food effect of RP-3500, a highly potent and specific inhibitor of ataxia telangiectasia and Rad3-related (ATR) protein kinase in patients (pts) with cancer

Author

Lheureux, S., primary, Rosen, E., additional, Lee, E., additional, Spigel, D., additional, Højgaard, M., additional, Fontana, E., additional, Mettu, N.B., additional, Carter, L., additional, Patel, S., additional, Papp, R., additional, May, S., additional, Nejad, P., additional, Ulanet, D., additional, Wainszelbaum, M., additional, Manley, P., additional, Koehler, M., additional, Fretland, A.J., additional, Plummer, R., additional, and Yap, T.A., additional

Published
2022
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47. 5MO Comprehensive dose-finding strategy for single-agent RP-3500, a highly selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase

Author

Fontana, E., primary, Lee, E., additional, Rosen, E., additional, Spigel, D., additional, Højgaard, M., additional, Lheureux, S., additional, Mettu, N.B., additional, Carter, L., additional, Plummer, R., additional, Manley, P., additional, Ulanet, D., additional, Rimkunas, V., additional, Silverman, I.M., additional, O'Connell, J., additional, McDougall, R., additional, Wainszelbaum, M., additional, Xu, Y., additional, Koehler, M., additional, Fretland, A.J., additional, and Yap, T.A., additional

Published
2022
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48. 47P Prevalence of mutations in common tumour types in Northern England and utility of Experimental Cancer Medicine Centre (ECMC) CRUK Trial Finder

Author

Rae, S.C.A., primary, Plummer, E., additional, Fitzgerald, L., additional, Hogarth, L., additional, Bridgewood, A., additional, Brown-Schofield, L., additional, Graham, J., additional, Drew, Y., additional, Haris, N., additional, Bashir, S., additional, Plummer, R., additional, and Greystoke, A., additional

Published
2022
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49. 9P Preliminary population pharmacokinetic (popPK) co-variates and exposure response (ER) assessment of QT for RP-3500, a highly potent and specific inhibitor of ataxia telangiectasia and Rad3-related (ATR) protein kinase

Author

Lee, E., primary, Yap, T.A., additional, Fontana, E., additional, Rosen, E., additional, Spigel, D., additional, Lheureux, S., additional, Mettu, N.B., additional, Carter, L., additional, Plummer, R., additional, Patel, S., additional, McDougall, R., additional, Papp, R., additional, May, S., additional, Nejad, P., additional, Ulanet, D., additional, Wainszelbaum, M., additional, Manley, P., additional, Koehler, M., additional, Fretland, A.J., additional, and Højgaard, M., additional

Published
2022
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50. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, Bickel, R, Biener, J, Biesiada, T, Bigelow, K, Bigelow-Granillo, J, Bigman, V, Bionta, RM, Birge, NW, Bitter, M, Black, AC, Bleile, R, Bleuel, DL, Bliss, E, Blue, B, Boehly, T, Boehm, K, Boley, CD, Bonanno, R, Bond, EJ, Bond, T, Bonino, MJ, Borden, M, Bourgade, J-L, Bousquet, J, Bowers, J, Bowers, M, Boyd, R, Bozek, A, Bradley, DK, Bradley, KS, Bradley, PA, Bradley, L, Brannon, L, Brantley, PS, Braun, D, Braun, T, Brienza-Larsen, K, Briggs, TM, Britten, J, Brooks, ED, Browning, D, Bruhn, MW, Brunner, TA, Bruns, H, Brunton, G, Bryant, B, Buczek, T, Bude, J, Buitano, L, Burkhart, S, Burmark, J, Burnham, A, Burr, R, Busby, LE, Butlin, B, Cabeltis, R, Cable, M, Cabot, WH, Cagadas, B, Caggiano, J, Cahayag, R, Caldwell, SE, Calkins, S, Callahan, DA, Calleja-Aguirre, J, Camara, L, Camp, D, Campbell, EM, Campbell, JH, Carey, B, Carey, R, Carlisle, K, Carlson, L, Carman, L, Carmichael, J, Carpenter, A, Carr, C, Carrera, JA, Casavant, D, Casey, A, Casey, DT, Castillo, A, Castillo, E, Castor, JI, Castro, C, Caughey, W, Cavitt, R, Celeste, J, Celliers, PM, Cerjan, C, Chandler, G, Chang, B, Chang, C, Chang, J, Chang, L, Chapman, R, Chapman, T, Chase, L, Chen, H, Chen, K, Chen, L-Y, Cheng, B, Chittenden, J, Choate, C, Chou, J, Chrien, RE, Chrisp, M, Christensen, K, Christensen, M, Christopherson, AR, Chung, M, Church, JA, Clark, A, Clark, DS, Clark, K, Clark, R, Claus, L, Cline, B, Cline, JA, Cobble, JA, Cochrane, K, Cohen, B, Cohen, S, Collette, MR, Collins, G, Collins, LA, Collins, TJB, Conder, A, Conrad, B, Conyers, M, Cook, AW, Cook, D, Cook, R, Cooley, JC, Cooper, G, Cope, T, Copeland, SR, Coppari, F, Cortez, J, Cox, J, Crandall, DH, Crane, J, Craxton, RS, Cray, M, Crilly, A, Crippen, JW, Cross, D, Cuneo, M, Cuotts, G, Czajka, CE, Czechowicz, D, Daly, T, Danforth, P, Darbee, R, Darlington, B, Datte, P, Dauffy, L, Davalos, G, Davidovits, S, Davis, P, Davis, J, Dawson, S, Day, RD, Day, TH, Dayton, M, Deck, C, Decker, C, Deeney, C, DeFriend, KA, Deis, G, Delamater, ND, Delettrez, JA, Demaret, R, Demos, S, Dempsey, SM, Desjardin, R, Desjardins, T, Desjarlais, MP, Dewald, EL, DeYoreo, J, Diaz, S, Dimonte, G, Dittrich, TR, Divol, L, Dixit, SN, Dixon, J, Dodd, ES, Dolan, D, Donovan, A, Donovan, M, Döppner, T, Dorrer, C, Dorsano, N, Douglas, MR, Dow, D, Downie, J, Downing, E, Dozieres, M, Draggoo, V, Drake, D, Drake, RP, Drake, T, Dreifuerst, G, DuBois, DF, DuBois, PF, Dunham, G, Dylla-Spears, R, Dymoke-Bradshaw, AKL, Dzenitis, B, Ebbers, C, Eckart, M, Eddinger, S, Eder, D, Edgell, D, Edwards, MJ, Efthimion, P, Eggert, JH, Ehrlich, B, Ehrmann, P, Elhadj, S, Ellerbee, C, Elliott, NS, Ellison, CL, Elsner, F, Emerich, M, Engelhorn, K, England, T, English, E, Epperson, P, Epstein, R, Erbert, G, Erickson, MA, Erskine, DJ, Erlandson, A, Espinosa, RJ, Estes, C, Estabrook, KG, Evans, S, Fabyan, A, Fair, J, Fallejo, R, Farmer, N, Farmer, WA, Farrell, M, Fatherley, VE, Fedorov, M, Feigenbaum, E, Feit, M, Ferguson, W, Fernandez, JC, Fernandez-Panella, A, Fess, S, Field, JE, Filip, CV, Fincke, JR, Finn, T, Finnegan, SM, Finucane, RG, Fischer, M, Fisher, A, Fisher, J, Fishler, B, Fittinghoff, D, Fitzsimmons, P, Flegel, M, Flippo, KA, Florio, J, Folta, J, Folta, P, Foreman, LR, Forrest, C, Forsman, A, Fooks, J, Foord, M, Fortner, R, Fournier, K, Fratanduono, DE, Frazier, N, Frazier, T, Frederick, C, Freeman, MS, Frenje, J, Frey, D, Frieders, G, Friedrich, S, Froula, DH, Fry, J, Fuller, T, Gaffney, J, Gales, S, Le Galloudec, B, Le Galloudec, KK, Gambhir, A, Gao, L, Garbett, WJ, Garcia, A, Gates, C, Gaut, E, Gauthier, P, Gavin, Z, Gaylord, J, Geissel, M, Génin, F, Georgeson, J, Geppert-Kleinrath, H, Geppert-Kleinrath, V, Gharibyan, N, Gibson, J, Gibson, C, Giraldez, E, Glebov, V, Glendinning, SG, Glenn, S, Glenzer, SH, Goade, S, Gobby, PL, Goldman, SR, Golick, B, Gomez, M, Goncharov, V, Goodin, D, Grabowski, P, Grafil, E, Graham, P, Grandy, J, Grasz, E, Graziani, F, Greenman, G, Greenough, JA, Greenwood, A, Gregori, G, Green, T, Griego, JR, Grim, GP, Grondalski, J, Gross, S, Guckian, J, Guler, N, Gunney, B, Guss, G, Haan, S, Hackbarth, J, Hackel, L, Hackel, R, Haefner, C, Hagmann, C, Hahn, KD, Hahn, S, Haid, BJ, Haines, BM, Hall, BM, Hall, C, Hall, GN, Hamamoto, M, Hamel, S, Hamilton, CE, Hammel, BA, Hammer, JH, Hampton, G, Hamza, A, Handler, A, Hansen, S, Hanson, D, Haque, R, Harding, D, Harding, E, Hares, JD, Harris, DB, Harte, JA, Hartouni, EP, Hatarik, R, Hatchett, S, Hauer, AA, Havre, M, Hawley, R, Hayes, J, Hayes, S, Hayes-Sterbenz, A, Haynam, CA, Haynes, DA, Headley, D, Heal, A, Heebner, JE, Heerey, S, Heestand, GM, Heeter, R, Hein, N, Heinbockel, C, Hendricks, C, Henesian, M, Heninger, J, Henrikson, J, Henry, EA, Herbold, EB, Hermann, MR, Hermes, G, Hernandez, JE, Hernandez, VJ, Herrmann, MC, Herrmann, HW, Herrera, OD, Hewett, D, Hibbard, R, Hicks, DG, Hill, D, Hill, K, Hilsabeck, T, Hinkel, DE, Ho, DD, Ho, VK, Hoffer, JK, Hoffman, NM, Hohenberger, M, Hohensee, M, Hoke, W, Holdener, D, Holdener, F, Holder, JP, Holko, B, Holunga, D, Holzrichter, JF, Honig, J, Hoover, D, Hopkins, D, Berzak Hopkins, L, Hoppe, M, Hoppe, ML, Horner, J, Hornung, R, Horsfield, CJ, Horvath, J, Hotaling, D, House, R, Howell, L, Hsing, WW, Hu, SX, Huang, H, Huckins, J, Hui, H, Humbird, KD, Hund, J, Hunt, J, Hurricane, OA, Hutton, M, Huynh, KH-K, Inandan, L, Iglesias, C, Igumenshchev, IV, Izumi, N, Jackson, M, Jackson, J, Jacobs, SD, James, G, Jancaitis, K, Jarboe, J, Jarrott, LC, Jasion, D, Jaquez, J, Jeet, J, Jenei, AE, Jensen, J, Jimenez, J, Jimenez, R, Jobe, D, Johal, Z, Johns, HM, Johnson, D, Johnson, MA, Gatu Johnson, M, Johnson, RJ, Johnson, S, Johnson, SA, Johnson, T, Jones, K, Jones, O, Jones, M, Jorge, R, Jorgenson, HJ, Julian, M, Jun, BI, Jungquist, R, Kaae, J, Kabadi, N, Kaczala, D, Kalantar, D, Kangas, K, Karasiev, VV, Karasik, M, Karpenko, V, Kasarky, A, Kasper, K, Kauffman, R, Kaufman, MI, Keane, C, Keaty, L, Kegelmeyer, L, Keiter, PA, Kellett, PA, Kellogg, J, Kelly, JH, Kemic, S, Kemp, AJ, Kemp, GE, Kerbel, GD, Kershaw, D, Kerr, SM, Kessler, TJ, Key, MH, Khan, SF, Khater, H, Kiikka, C, Kilkenny, J, Kim, Y, Kim, Y-J, Kimko, J, Kimmel, M, Kindel, JM, King, J, Kirkwood, RK, Klaus, L, Klem, D, Kline, JL, Klingmann, J, Kluth, G, Knapp, P, Knauer, J, Knipping, J, Knudson, M, Kobs, D, Koch, J, Kohut, T, Kong, C, Koning, JM, Koning, P, Konior, S, Kornblum, H, Kot, LB, Kozioziemski, B, Kozlowski, M, Kozlowski, PM, Krammen, J, Krasheninnikova, NS, Kraus, B, Krauser, W, Kress, JD, Kritcher, AL, Krieger, E, Kroll, JJ, Kruer, WL, Kruse, MKG, Kucheyev, S, Kumbera, M, Kumpan, S, Kunimune, J, Kustowski, B, Kwan, TJT, Kyrala, GA, Laffite, S, Lafon, M, LaFortune, K, Lahmann, B, Lairson, B, Landen, OL, Langenbrunner, J, Lagin, L, Land, T, Lane, M, Laney, D, Langdon, AB, Langer, SH, Langro, A, Lanier, NE, Lanier, TE, Larson, D, Lasinski, BF, Lassle, D, LaTray, D, Lau, G, Lau, N, Laumann, C, Laurence, A, Laurence, TA, Lawson, J, Le, HP, Leach, RR, Leal, L, Leatherland, A, LeChien, K, Lechleiter, B, Lee, A, Lee, M, Lee, T, Leeper, RJ, Lefebvre, E, Leidinger, J-P, LeMire, B, Lemke, RW, Lemos, NC, Le Pape, S, Lerche, R, Lerner, S, Letts, S, Levedahl, K, Lewis, T, Li, CK, Li, H, Li, J, Liao, W, Liao, ZM, Liedahl, D, Liebman, J, Lindford, G, Lindman, EL, Lindl, JD, Loey, H, London, RA, Long, F, Loomis, EN, Lopez, FE, Lopez, H, Losbanos, E, Loucks, S, Lowe-Webb, R, Lundgren, E, Ludwigsen, AP, Luo, R, Lusk, J, Lyons, R, Ma, T, Macallop, Y, MacDonald, MJ, MacGowan, BJ, Mack, JM, Mackinnon, AJ, MacLaren, SA, MacPhee, AG, Magelssen, GR, Magoon, J, Malone, RM, Malsbury, T, Managan, R, Mancini, R, Manes, K, Maney, D, Manha, D, Mannion, OM, Manuel, AM, Mapoles, E, Mara, G, Marcotte, T, Marin, E, Marinak, MM, Mariscal, C, Mariscal, DA, Mariscal, EF, Marley, EV, Marozas, JA, Marquez, R, Marshall, CD, Marshall, FJ, Marshall, M, Marshall, S, Marticorena, J, Martinez, D, Maslennikov, I, Mason, D, Mason, RJ, Masse, L, Massey, W, Masson-Laborde, P-E, Masters, ND, Mathisen, D, Mathison, E, Matone, J, Matthews, MJ, Mattoon, C, Mattsson, TR, Matzen, K, Mauche, CW, Mauldin, M, McAbee, T, McBurney, M, Mccarville, T, McCrory, RL, McEvoy, AM, McGuffey, C, Mcinnis, M, McKenty, P, McKinley, MS, McLeod, JB, McPherson, A, Mcquillan, B, Meamber, M, Meaney, KD, Meezan, NB, Meissner, R, Mehlhorn, TA, Mehta, NC, Menapace, J, Merrill, FE, Merritt, BT, Merritt, EC, Meyerhofer, DD, Mezyk, S, Mich, RJ, Michel, PA, Milam, D, Miller, C, Miller, D, Miller, DS, Miller, E, Miller, EK, Miller, J, Miller, M, Miller, PE, Miller, T, Miller, W, Miller-Kamm, V, Millot, M, Milovich, JL, Minner, P, Miquel, J-L, Mitchell, S, Molvig, K, Montesanti, RC, Montgomery, DS, Monticelli, M, Montoya, A, Moody, JD, Moore, AS, Moore, E, Moran, M, Moreno, JC, Moreno, K, Morgan, BE, Morrow, T, Morton, JW, Moses, E, Moy, K, Muir, R, Murillo, MS, Murray, JE, Murray, JR, Munro, DH, Murphy, 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Subjects
General Physics, 02 Physical Sciences, General Physics and Astronomy, Indirect Drive ICF Collaboration, 01 Mathematical Sciences, 09 Engineering
Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022

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