NEW YORK – Precision medicine company Ideaya Biosciences said on Wednesday that it is collaborating with Pfizer in an upcoming clinical trial evaluating IDE196 in combination with MEK inhibitor binimetinib (Pfizer/Array Biopharma's Mektovi) for patients with GNAQ or GNA11 hotspot-mutated solid tumors such as uveal melanoma and colorectal cancer. The companies expect the trial to start in mid-2020.
IDE196 is an investigational PKC inhibitor Ideaya licensed from Novartis. PKC is involved in signal transductions that can impact the survival of cells with active mutations in GNAQ or GNA11. These mutations are found in about 90 percent of uveal melanomas, which are cancers of the eye. These patients tend to have a poor prognosis, and primary treatment options are typically radiation therapy, laser therapy, or surgery.
The drug is currently being studied as a monotherapy in a Phase I/II basket trial for solid tumors harboring GNAQ/11 mutations or PRKC fusions. IDE196 has reportedly demonstrated early clinical activity and tolerability in an ongoing Phase I clinical study being conducted by Novartis in patients with metastatic uveal melanoma (MUM).
Binimetinib was previously approved alongside encorafenib (Pfizer/Array BioPharma's Braftovi) for BRAF V600E or V600K-mutated melanoma. Binimetinib has also been studied in various combinations for treating metastatic colorectal cancer.
The new clinical combination study with Pfizer will evaluate whether inhibition of the MAP-Kinase pathway through upstream PKC and downstream MEK inhibition will improve response rate and outcomes in patients whose solid tumors have GNAQ or GNA11 hotspot mutations.
"The prevalence of GNAQ or GNA11 hotspot mutations in MUM, Cutaneous Melanoma, CRC, and other solid tumors represents approximately 6,000 patients in the US and the five major European countries, and there are no approved targeted therapies for MUM or GNAQ/GNA11 hotspot mutation solid tumors," Ideaya's CEO Yujiro S. Hata said in a statement.
Ideaya has noted on its company website that 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.