| Autor: |
S. Piperno-Neumann, M. S. Carlino, V. Boni, D. Loirat, F. M. Speetjens, J. J. Park, E. Calvo, R. D. Carvajal, M. Nyakas, J. Gonzalez-Maffe, X. Zhu, M. D. Shirley, T. Ramkumar, A. Fessehatsion, H. E. Burks, P. Yerramilli-Rao, E. Kapiteijn |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
British Journal of Cancer, 128, 1040-1051. SPRINGERNATURE |
| Popis: |
Background Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. Methods This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100–1000 mg once daily (QD; n = 38) and 200–400 mg twice daily (BID; n = 30). Results First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81–15.28) for QD and 4.6 months (range: 0.33–58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99–41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. Conclusion These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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