Search

Your search keyword '"Yuen, Eunice"' showing total 350 results
Start Over Author "Yuen, Eunice"
350 results on '"Yuen, Eunice"'

2. Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study.

Author

Bhave, Manali A., primary, Jhaveri, Komal L., additional, Kaufman, Peter A., additional, Aftimos, Philippe Georges, additional, Lombard, Janine Margaret, additional, Sideras, Kostandinos, additional, Im, Seock-Ah, additional, Ma, Cynthia X., additional, Lee, Kuo-Ting, additional, Kim, Sung-Bae, additional, Li, Yujia, additional, Yuen, Eunice, additional, Estrem, Shawn T., additional, Nguyen, Bastien, additional, Bacchion, Francesca, additional, Ismail-Khan, Roohi, additional, Beeram, Muralidhar, additional, and Sohn, Joohyuk, additional

Published
2024
Full Text
View/download PDF

20. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors.

Author

Garralda, Elena, Schram, Alison M, Bedard, Philippe L, Schwartz, Gary K, Yuen, Eunice, McNeely, Samuel C, Ribeiro, Silvia, Cunningham, Jason, Wang, Yi, Urunuela, Arantxa, Xu, Xiaojian, and LoRusso, Patricia

Subjects
THERAPEUTIC use of antineoplastic agents, DRUG efficacy, DRUG dosage, DRUG tolerance, CLINICAL trials, DIARRHEA, NAUSEA, PROTEIN kinase inhibitors, ANTINEOPLASTIC agents, GASTROINTESTINAL diseases, CANCER patients, VOMITING, ASTHENIA, CELL cycle, RESEARCH funding, DESCRIPTIVE statistics, ANEMIA, PLATELET count, GENE expression profiling, TUMORS, FATIGUE (Physiology), ABDOMINAL pain, PATIENT safety, DRUG toxicity
Abstract

Background This study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors. Materials and Methods LY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity. Results Fifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n  = 3; 35 mg: n  = 3; 25 mg: n  = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed. Conclusion The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development. ClinicalTrials.gov Identifier NCT03770494. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

21. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors

Author

Garralda, Elena, primary, Schram, Alison M, additional, Bedard, Philippe L, additional, Schwartz, Gary K, additional, Yuen, Eunice, additional, McNeely, Samuel C, additional, Ribeiro, Silvia, additional, Cunningham, Jason, additional, Wang, Yi, additional, Urunuela, Arantxa, additional, Xu, Xiaojian, additional, and LoRusso, Patricia, additional

Published
2023
Full Text
View/download PDF

23. Contributors

Author

Abyzov, Alexej, primary, Allan, Kevin Cameron, additional, Amiri, Anahita, additional, Brown, Heather M., additional, Calof, Anne L., additional, Chang, Qiang, additional, Christian, Kimberly M., additional, Clayton, Benjamin L.L., additional, Cucinotta, Francesca, additional, D'Gama, Alissa M., additional, Elitt, Mathew Sean, additional, Fernandez, L., additional, Fitch, R. Holly, additional, Golden, Jeffrey A., additional, Groves, Laura, additional, Hagerman, R.J., additional, Jaffe, Eric, additional, Johnson-Kerner, B.L., additional, Jourdon, Alexandre, additional, Lander, Arthur D., additional, Leigh, M.J., additional, Lim, Youngshin, additional, Mahnke, A.H., additional, Mariani, Jessica, additional, Ming, Guo-li, additional, Miranda, R.C., additional, Mooney, S.M., additional, Neul, Jeffrey L., additional, Nevin, Zachary Scott, additional, Niswander, Lee, additional, Oliver, Christopher, additional, Persico, Antonio M., additional, Pezoa, Sofia A., additional, Pyrgaki, Christina, additional, Reiter, Lawrence T., additional, Ricciardello, Arianna, additional, Rubenstein, Edward, additional, Sahin, Mustafa, additional, Santos, Rosaysela, additional, Scuderi, Soraya, additional, Sherr, E.H., additional, Song, Hongjun, additional, Srivastava, Siddharth, additional, Tesar, Paul J., additional, Turriziani, Laura, additional, Vaccarino, Flora M., additional, Walsh, Christopher A., additional, Wu, Feinan, additional, and Yuen, Eunice Y., additional

Published
2020
Full Text
View/download PDF

25. Application of population pharmacokinetic/pharmacodynamic methodologies to current clinical issues facing drug development

Author

Yuen, Eunice Soek Mun and Aarons, Leon

Subjects
615.1
Abstract

Pharmaceutical drug development is a lengthy process and has been associated with rising development costs. Modelling and simulation (M&S) approaches employed across preclinical development phases to phase IV provide an evolving quantitative framework and thus may speed up this process. In this thesis, some population PK/PD M&S techniques to aid in dose optimisation and trial simulations applied to some current clinical issues in drug development are explored and presented. In the area of pharmacogenetics and personalised medicine, warfarin was used as an example, where ethnic differences were initially observed in maintenance dose requirements. It was later found that this might be attributed to the differences in VKORC1 haplotype frequency distribution. Empirical PK/PD modelling showed that whilst CYP2C9 genotype status was predictive of S-warfarin clearance, VKORC1 haplotype status was more predictive of warfarin response. The models presented illustrate a starting point to characterise the pharmacogenetics effects on drug PK and PD. Together with the inclusion of more patient relevant characteristics, these may be used to assess the need for dose optimisation and personalised medicine. The integration of PK and PD data in a drug-disease model was illustrated through a meta-analysis of 3 phase III trials investigating the use of duloxetine in the treatment of diabetic peripheral neuropathy. Two population PK/PD models were developed: a continuous descriptive model for pain score reduction on the 11-point Likert scale and a proportional odds model describing the probability of achieving pain relief. The results from these models were similar to those presented in the literature for each trial. In addition, the agreement and definition of clinically meaningful pain relief between several efficacy scales against the patient global improvement (PGI) scale was explored. The results showed that whilst the mean difference between the scales was close to zero, precision was poor. By defining clinically meaningful pain relief as at least ‘much better’ on the PGI scale, the equivalent on the Likert scale was a minimum of 2.90 points, in agreement with previous literature findings. These analyses identifying correlations between scales provide opportunities for clinical validation and enable more accurate extrapolation of clinical data across studies. Missing data is present in most clinical trials. Since PK/PD models are frequently developed using non-missing longitudinal data, the influence of missing data on accuracy of parameter estimations should be investigated. This can be achieved through comparing different missing data imputation methods on the estimated parameters. The analysis results showed that regardless of imputation method, PK/PD parameter estimates were largely similar to those estimated with non-missing data, suggesting that missing data had little impact at an overall completion rate of approximately 75%. Selection models incorporating dropout were also developed to enable more accurate trial simulations. The results showed that the dropout mechanism was likely to be missing at random, and non-inclusion of dropout may lead to underestimation of variability and therefore the estimation of effect size. This thesis presented only a small subset of areas in which PK/PD M&S can play a role in drug development by focusing on some of the issues and challenges that currently face this process. Since M&S methodologies bridge across various disciplines, it should be well-placed to help handle any future issues that might face the development of pharmaceuticals.

Published
2011

27. Supplementary Methods from ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine

Author

Bhagwat, Shripad V., primary, McMillen, William T., primary, Cai, Shufen, primary, Zhao, Baohui, primary, Whitesell, Matthew, primary, Shen, Weihua, primary, Kindler, Lisa, primary, Flack, Robert S., primary, Wu, Wenjuan, primary, Anderson, Bryan, primary, Zhai, Yan, primary, Yuan, Xiu-Juan, primary, Pogue, Meghann, primary, Van Horn, Robert D., primary, Rao, Xi, primary, McCann, Denis, primary, Dropsey, Andrew J., primary, Manro, Jason, primary, Walgren, Jennie, primary, Yuen, Eunice, primary, Rodriguez, Michael J., primary, Plowman, Gregory D., primary, Tiu, Ramon V., primary, Joseph, Sajan, primary, and Peng, Sheng-Bin, primary

Published
2023
Full Text
View/download PDF

28. Data from ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine

Author

Bhagwat, Shripad V., primary, McMillen, William T., primary, Cai, Shufen, primary, Zhao, Baohui, primary, Whitesell, Matthew, primary, Shen, Weihua, primary, Kindler, Lisa, primary, Flack, Robert S., primary, Wu, Wenjuan, primary, Anderson, Bryan, primary, Zhai, Yan, primary, Yuan, Xiu-Juan, primary, Pogue, Meghann, primary, Van Horn, Robert D., primary, Rao, Xi, primary, McCann, Denis, primary, Dropsey, Andrew J., primary, Manro, Jason, primary, Walgren, Jennie, primary, Yuen, Eunice, primary, Rodriguez, Michael J., primary, Plowman, Gregory D., primary, Tiu, Ramon V., primary, Joseph, Sajan, primary, and Peng, Sheng-Bin, primary

Published
2023
Full Text
View/download PDF

29. Supplementary Figure S4 from ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine

Author

Bhagwat, Shripad V., primary, McMillen, William T., primary, Cai, Shufen, primary, Zhao, Baohui, primary, Whitesell, Matthew, primary, Shen, Weihua, primary, Kindler, Lisa, primary, Flack, Robert S., primary, Wu, Wenjuan, primary, Anderson, Bryan, primary, Zhai, Yan, primary, Yuan, Xiu-Juan, primary, Pogue, Meghann, primary, Van Horn, Robert D., primary, Rao, Xi, primary, McCann, Denis, primary, Dropsey, Andrew J., primary, Manro, Jason, primary, Walgren, Jennie, primary, Yuen, Eunice, primary, Rodriguez, Michael J., primary, Plowman, Gregory D., primary, Tiu, Ramon V., primary, Joseph, Sajan, primary, and Peng, Sheng-Bin, primary

Published
2023
Full Text
View/download PDF

30. Supplementary Table S3 from ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine

Author

Bhagwat, Shripad V., primary, McMillen, William T., primary, Cai, Shufen, primary, Zhao, Baohui, primary, Whitesell, Matthew, primary, Shen, Weihua, primary, Kindler, Lisa, primary, Flack, Robert S., primary, Wu, Wenjuan, primary, Anderson, Bryan, primary, Zhai, Yan, primary, Yuan, Xiu-Juan, primary, Pogue, Meghann, primary, Van Horn, Robert D., primary, Rao, Xi, primary, McCann, Denis, primary, Dropsey, Andrew J., primary, Manro, Jason, primary, Walgren, Jennie, primary, Yuen, Eunice, primary, Rodriguez, Michael J., primary, Plowman, Gregory D., primary, Tiu, Ramon V., primary, Joseph, Sajan, primary, and Peng, Sheng-Bin, primary

Published
2023
Full Text
View/download PDF

33. Abstract PD13-12: PD13-12 Imlunestrant, an oral selective estrogen receptor degrader, in combination with abemaciclib with or without an aromatase inhibitor, in estrogen receptor-positive advanced breast cancer: Results from the phase 1a/b EMBER study

Author

Jhaveri, Komal, primary, Wang, Hwei-Chung, additional, Ma, Cynthia, additional, Lim, Elgene, additional, Tao, Jessica J., additional, Manso, Luis, additional, Pierga, Jean-Yves, additional, Parajuli, Ritesh, additional, Gilarranz, Yolanda Jerez, additional, Lu, Yen-Shen, additional, Beeram, Muralidhar, additional, Larson, Tim, additional, Dhakal, Ajay, additional, Ismail-Khan, Roohi, additional, Karacsonyi, Claudia, additional, Cao, Shanshan, additional, Osborne, Cynthia, additional, Estrem, Shawn T., additional, Nguyen, Bastien, additional, Li, Yujia, additional, and Yuen, Eunice, additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results