Abstract CT068: A Phase I trial of LXS196, a novel PKC inhibitor for metastatic uveal melanoma

@article{Kapiteijn2019AbstractCA,
  title={Abstract CT068: A Phase I trial of LXS196, a novel PKC inhibitor for metastatic uveal melanoma},
  author={Ellen H W Kapiteijn and Matteo S Carlino and Valentina Boni and Delphine Loirat and Frank M Speetjens and John J Park and Emiliano Calvo and Richard D. Carvajal and Marta Nyakas and Juan Gonzalez-Maffe and Xu Zhu and Ramu Thiruvamoor and Padmaja Yerramilli-Rao and Sophie Piperno-Neumann},
  journal={Clinical Trials},
  year={2019}
}
We assessed the safety, tolerability, PK, PD and efficacy of the PKC inhibitor LXS196 in patients with metastatic uveal melanoma (MUM). As of 30 Sep 2018, 68 patients received LXS196 at doses ranging from 100 to 1000 mg once daily (QD; 38 patients) and 200 to 400 mg twice daily (BID; 30 patients). All patients in the QD regimen had discontinued treatment due to progressive disease. Five patients in the BID regimen remain on study. LDH was > ULN in 38 patients (55.9%), and 60 patients (88.2… 
4 Citations
Functional characterization of uveal melanoma oncogenes
TLDR
It is shown that the PKC/RasGRP3/MAPK signaling branch is the essential component that drives the proliferation of UM and is highlighted as the central signaling axis to be suppressed pharmacologically to treat for neoplastic disorders with Gαq pathway mutations.
GNAQ and GNA11 Genes: A Comprehensive Review on Oncogenesis, Prognosis and Therapeutic Opportunities in Uveal Melanoma
TLDR
This review aims to provide a current comprehensive view of what the authors know about GNAQ and GNA11 genes on oncogenesis, prognosis and therapeutic opportunities in uveal melanoma.
Equivocal, explicit and emergent actions of PKC isoforms in cancer
TLDR
This Review discusses protein kinase C (PKC) isoforms in cancer, in particular focusing on their functional properties in the context of tumour suppression or promotion, target validation, PKC pharmacology and therapeutic exploitation.