On October 16, 2023 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported initiation of a Phase 2 expansion of the darovasertib and crizotinib combination in GNAQ/11 metastatic cutaneous melanoma (Press release, Ideaya Biosciences, OCT 16, 2023, View Source [SID1234636029]).

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"We are pleased to advance the darovasertib and crizotinib combination into a Phase 2 expansion for GNAQ/11 metastatic cutaneous melanoma, where there are currently no FDA approved therapies in this genetically-defined patient population highlighting the unmet medical need," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. "As IDEAYA advances the registrational trial for darovasertib in first-line HLA-A2-negative metastatic uveal melanoma, it’s a strategic priority to expand the program’s clinical application in multiple solid tumor settings, including HLA-A2-positive metastatic uveal melanoma, neoadjuvant and adjuvant uveal melanoma, and GNAQ/11 cutaneous melanoma," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences.

"The clinical efficacy observed in a GNAQ melanoma patient that progressed on immune checkpoint inhibitor therapies and treated in our clinic has been durable and well tolerated. This is a very important finding in this biomarker defined population," said Dr. Marcus Butler, M.D., Medical Oncologist, Tumor Immunotherapy Program, Melanoma/Skin Oncology Site Lead at Princess Margaret Cancer Centre in Toronto, Canada, and Ocular Melanoma Physician Task Force of Canada Co-Lead.

The Phase 2 darovasertib and crizotinib combination expansion is based on preliminary clinical efficacy observed in the GNAQ/11 metastatic cutaneous melanoma setting. The GNAQ/11 prevalence in cutaneous melanoma has been reported at approximately 5% in The Cancer Genome Atlas. The GNAQ/11 cutaneous melanoma estimated annual incidence is approximately 5,000 patients in the US and 8,000 patients in the EU28, and the estimated total prevalence of GNAQ/11 cutaneous melanoma is approximately 70,000 patients in the US and 110,000 patients in the EU28. It has been reported that approximately 12.5% to 15% of cutaneous melanoma patients have been reported to develop metastatic disease, whereas in uveal melanoma, a predominantly GNAQ/11 mediated cancer, the metastatic rate has been reported at approximately 50%. In addition, based on several metastatic cancer patient databases, including Memorial Sloan Kettering Cancer Center (MSKCC) Impact, we project GNAQ/11 metastatic cutaneous melanoma has the potential to double or more the annual addressable metastatic patient population of metastatic uveal melanoma alone. In addition, GNAQ/11 mutation patients are known to have low tumor mutational burden making these patients less likely to benefit from immune checkpoint inhibitor therapies.

Darovasertib (IDE196) is a potent, selective small molecule inhibitor of protein kinase C (PKC). Mutations in GNAQ or GNA11 (GNAQ/11) have been identified in approximately 90% of patients with metastatic uveal melanoma. These mutations are associated with activation of signaling pathways, including oncogenic RAS/RAF/MEK/ERK via PKC activation, driving tumor progression.