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21 results on '"Cleverly, Ann L."'

1. Supplemental Figure 1 from First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

Author

Rodon, Jordi, primary, Carducci, Michael A., primary, Sepulveda-Sánchez, Juan M, primary, Azaro, Analia, primary, Calvo, Emiliano, primary, Seoane, Joan, primary, Braña, Irene, primary, Sicart, Elisabet, primary, Gueorguieva, Ivelina, primary, Cleverly, Ann L., primary, Pillay, N. Sokalingum, primary, Desaiah, Durisala, primary, Estrem, Shawn T., primary, Paz-Ares, Luis, primary, Holdhoff, Matthias, primary, Blakeley, Jaishri, primary, Lahn, Michael M., primary, and Baselga, Jose, primary

Published
2023
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2. Data from Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes

Author

Santini, Valeria, primary, Valcárcel, David, primary, Platzbecker, Uwe, primary, Komrokji, Rami S., primary, Cleverly, Ann L., primary, Lahn, Michael M., primary, Janssen, Jan, primary, Zhao, Yumin, primary, Chiang, Alan, primary, Giagounidis, Aristoteles, primary, Guba, Susan C., primary, Gueorguieva, Ivelina, primary, Girvan, Allicia C., primary, da Silva Ferreira, Mariana, primary, Bhagat, Tushar D., primary, Pradhan, Kith, primary, Steidl, Ulrich, primary, Sridharan, Ashwin, primary, Will, Britta, primary, and Verma, Amit, primary

Published
2023
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3. Supplementary Tables and Figures from Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes

Author

Santini, Valeria, primary, Valcárcel, David, primary, Platzbecker, Uwe, primary, Komrokji, Rami S., primary, Cleverly, Ann L., primary, Lahn, Michael M., primary, Janssen, Jan, primary, Zhao, Yumin, primary, Chiang, Alan, primary, Giagounidis, Aristoteles, primary, Guba, Susan C., primary, Gueorguieva, Ivelina, primary, Girvan, Allicia C., primary, da Silva Ferreira, Mariana, primary, Bhagat, Tushar D., primary, Pradhan, Kith, primary, Steidl, Ulrich, primary, Sridharan, Ashwin, primary, Will, Britta, primary, and Verma, Amit, primary

Published
2023
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4. Legend for Supplementary Figure 1 from First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

Author

Rodon, Jordi, primary, Carducci, Michael A., primary, Sepulveda-Sánchez, Juan M, primary, Azaro, Analia, primary, Calvo, Emiliano, primary, Seoane, Joan, primary, Braña, Irene, primary, Sicart, Elisabet, primary, Gueorguieva, Ivelina, primary, Cleverly, Ann L., primary, Pillay, N. Sokalingum, primary, Desaiah, Durisala, primary, Estrem, Shawn T., primary, Paz-Ares, Luis, primary, Holdhoff, Matthias, primary, Blakeley, Jaishri, primary, Lahn, Michael M., primary, and Baselga, Jose, primary

Published
2023
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8. Safety, tolerability, QTc evaluation, and pharmacokinetics of single and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-β inhibitor, in healthy subjects

Author

Welch, Pamela A., Sinha, Vikram P., Cleverly, Ann L., Darstein, Christelle, Flanagan, Shawn D., and Musib, Luna C.

Subjects
Pharmacokinetics -- Research -- Physiological aspects, Heart beat -- Physiological aspects -- Research, Enzyme inhibitors -- Dosage and administration -- Properties -- Research, Health, Physiological aspects, Research, Properties, Dosage and administration
Abstract

The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) [...]

Published
2007

9. Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes

Author

Santini, Valeria, primary, Valcárcel, David, additional, Platzbecker, Uwe, additional, Komrokji, Rami S., additional, Cleverly, Ann L., additional, Lahn, Michael M., additional, Janssen, Jan, additional, Zhao, Yumin, additional, Chiang, Alan, additional, Giagounidis, Aristoteles, additional, Guba, Susan C., additional, Gueorguieva, Ivelina, additional, Girvan, Allicia C., additional, da Silva Ferreira, Mariana, additional, Bhagat, Tushar D., additional, Pradhan, Kith, additional, Steidl, Ulrich, additional, Sridharan, Ashwin, additional, Will, Britta, additional, and Verma, Amit, additional

Published
2019
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10. P1‐326: THE USE OF THE DIGITAL CLOCK DRAWING TEST (DCTCLOCK™) IN THE SCREENING PHASE OF CLINICAL TRIALS FOR ALZHEIMER'S DISEASE

Author

Dage, Jeffrey L., primary, Battioui, Chakib, additional, Wang, Jian WJ., additional, Charil, Arnaud, additional, Shcherbinin, Sergey, additional, Lowe, Stephen L., additional, Lo, Albert, additional, Cleverly, Ann L., additional, Schwarz, Adam J., additional, Irizarry, Michael C., additional, and Miller, Bradley B., additional

Published
2018
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11. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

Author

Lahn, Michael, Herbertz,Stephan, Sawyer,J. Scott, Stauber,Anja J, Gueorguieva,Ivelina, Driscoll,Kyla E, Estrem,Shawn T, Cleverly,Ann L, Desaiah,Durisala, Guba,Susan, Benhadji,Karim A, and Slapak,Christopher A

Subjects
Drug Design, Development and Therapy
Abstract

Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle) of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens (including nivolumab) in patients with cancer with high unmet medical needs such as glioblastoma, pancreatic cancer, and hepatocellular carcinoma. The present review summarizes the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. Keywords: TGF-β, TGF-βRI kinase inhibitor, ALK5, galunisertib, LY2157299, cancer, clinical trials

Published
2015

12. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

Author

Herbertz,Stephan, Sawyer,J Scott, Stauber,Anja J, Gueorguieva,Ivelina, Driscoll,Kyla E, Estrem,Shawn T, Cleverly,Ann L, Desaiah,Durisala, Guba,Susan, Benhadji,Karim A, Slapak,Christopher A, Lahn,Michael, Herbertz,Stephan, Sawyer,J Scott, Stauber,Anja J, Gueorguieva,Ivelina, Driscoll,Kyla E, Estrem,Shawn T, Cleverly,Ann L, Desaiah,Durisala, Guba,Susan, Benhadji,Karim A, Slapak,Christopher A, and Lahn,Michael

Abstract

Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3 Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle) of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens

Published
2015

14. Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes

Author

Valcarcel, David, primary, Verma, Amit, additional, Platzbecker, Uwe, additional, Santini, Valeria, additional, Giagounidis, Aristoteles, additional, Díez-Campelo, María, additional, Janssen, Jan, additional, Schlenk, Richard F., additional, Gaidano, Gianluca, additional, Perez de Oteyza, Jaime, additional, Cleverly, Ann L, additional, Chiang, Alan Y, additional, Lahn, Michael, additional, Desiaih, Durisala, additional, Guba, Susan C., additional, List, Alan F., additional, and Komrokji, Rami S., additional

Published
2015
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15. First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

Author

Rodon, Jordi, primary, Carducci, Michael A., additional, Sepulveda-Sánchez, Juan M, additional, Azaro, Analia, additional, Calvo, Emiliano, additional, Seoane, Joan, additional, Braña, Irene, additional, Sicart, Elisabet, additional, Gueorguieva, Ivelina, additional, Cleverly, Ann L., additional, Pillay, N. Sokalingum, additional, Desaiah, Durisala, additional, Estrem, Shawn T., additional, Paz-Ares, Luis, additional, Holdhoff, Matthias, additional, Blakeley, Jaishri, additional, Lahn, Michael M., additional, and Baselga, Jose, additional

Published
2015
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16. Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study

Author

Kovacs, Richard J., primary, Maldonado, Giuliana, additional, Azaro, Analia, additional, Fernández, Maria S., additional, Romero, Federico L., additional, Sepulveda-Sánchez, Juan M., additional, Corretti, Mary, additional, Carducci, Michael, additional, Dolan, Melda, additional, Gueorguieva, Ivelina, additional, Cleverly, Ann L., additional, Pillay, N. Sokalingum, additional, Baselga, Jose, additional, and Lahn, Michael M., additional

Published
2014
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17. A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer

Author

COHN, ALLEN, primary, LAHN, MICHAEL M., additional, WILLIAMS, KRISTEN E., additional, CLEVERLY, ANN L., additional, PITOU, CELINE, additional, KADAM, SUNIL K., additional, FARMEN, MARK W., additional, DESAIAH, DURISALA, additional, RAJU, ROBERT, additional, CONKLING, PAUL, additional, and RICHARDS, DONALD, additional

Published
2014
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18. Case Series of Cancer Patients Treated With Galunisertib, a Transforming Growth Factor-Beta Receptor I Kinase Inhibitor in a First-in-Human Dose Study

Author

Azaro, Analia, primary, Rodon, Jordi, additional, Carducci, Michael, additional, Sepulveda-Sanchez, Juan M., additional, Gueorguieva, Ivelina, additional, Cleverly, Ann L., additional, Desaiah, Durisala, additional, Namaseevayam, Sokalingum P., additional, Holdhoff, Matthias, additional, and Lahn, Michael M., additional

Published
2014
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21. Safety, tolerability, QTc evaluation, and pharmacokinetics of single and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-beta inhibitor, in healthy subjects.

Author

Welch PA, Sinha VP, Cleverly AL, Darstein C, Flanagan SD, and Musib LC

Subjects
Administration, Oral, Adolescent, Adult, Area Under Curve, Diarrhea chemically induced, Dose-Response Relationship, Drug, Drug Administration Schedule, Electrocardiography, Female, Half-Life, Headache chemically induced, Humans, Indoles administration & dosage, Indoles adverse effects, Male, Middle Aged, Nausea chemically induced, Protein Kinase C antagonists & inhibitors, Protein Kinase C beta, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Sleep drug effects, Indoles pharmacokinetics, Protein Kinase Inhibitors pharmacokinetics
Abstract

The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and its metabolites ranged from approximately 12 to 40 hours. The longer half-life of the major circulating and pharmacologically active metabolite allowed once-a-day dosing and predicted that steady state would be achieved within 2 weeks of daily oral dosing in all subjects. In the multiple-dose study, daily doses (25-400 mg) were examined, with 24 subjects receiving at least 1 dose. The most common adverse events related to enzastaurin were headache, sleepiness, diarrhea, and nausea. No clinically significant changes in QTc intervals were observed. Overall, enzastaurin was well tolerated in healthy subjects, and the planned maximum dose was achieved in both studies.

Published
2007
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