PKC (IDE196)


IDEAYA is developing IDE196, a protein kinase C (PKC) inhibitor, for the treatment of cancers with GNAQ and GNA11 activating mutations, which are prevalent in >90% of patients having metastatic uveal melanoma (MUM).

MUM is an orphan disease with a high unmet need and no current effective therapies. From 1998-2015, twenty-nine Phase 2 clinical studies demonstrated no material improvement in clinical outcomes. Notably, immune oncology agents have not been clinically active in this disease. At present for MUM, median PFS is 3.3 mo and median OS is 10.2 mo.

IDEAYA entered into an exclusive license agreement with Novartis to develop and commercialize Novartis’ LXS196, a Phase 1 protein kinase C (PKC) inhibitor for the treatment of cancers with GNAQ and GNA11 mutations.

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Clinical Development

IDE196 is a selective small molecule inhibitor of PKC, demonstrating early clinical activity and tolerability in an ongoing Phase 1 clinical study being conducted by Novartis in patients with metastatic uveal melanoma (MUM). This clinical trial is entitled “A Phase I, multi-center, open-label, study of LXS196, an oral protein kinase C inhibitor, in patients with metastatic uveal melanoma” ( Identifier: NCT02601378). In the ongoing trial, IDE196 is being studied as a single-agent and in combination therapy with HDM201, Novartis’ human double minute 2 (HDM2) inhibitor, an important negative regulator of the p53 tumor suppressor.

IDEAYA will continue clinical development of IDE196. In addition to MUM, IDEAYA will also explore a tumor agnostic basket study of solid tumors with mutations of GNAQ and GNA11. Both GNAQ and GNA11 mutations are listed in multiple diagnostic panels, including the FoundationOne CDx™ NGS panel, FoundationOne™Liquid Biopsy Panel, and the Guardant360® Liquid Biopsy panel, which provides a clear path towards identifying patients. IDEAYA is also evaluating the potential use of IDE196 to target various PKC fusion isoforms.

Preclinical Data

In the GNAQ mutant uveal melanoma cell-line xenograft, 92.1, LXS196 induces durable, dose-dependent tumor regressions with oral doses of 75 mg/kg BID and higher.

IDE196 Monotherapy In Vivo Efficacy

GNAQ mutant uveal melanoma cell-line xenograft, 92.1 (IDE196 and AEB071)