Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma

Piperno-Neumann, S, Carlino, M, Boni, V, Speetjens, FM, Park, JJ, Calvo, E, Carvajal, RD, Nyakas, M, Gonzalez Maffe, Juan, Zhu, Xu, Shirley, Matt, Ramkumar, Thiruvamoor, Fessehatsion, Adonai, Burks, Heather, Yerramilli-Rao, Padmaja and Kapiteijn, E (2023) A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma. British journal of cancer. ISSN 1532-1827


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.

Item Type: Article
Date Deposited: 08 Mar 2023 00:45
Last Modified: 08 Mar 2023 00:45


Email Alerts

Register with OAK to receive email alerts for saved searches.