darovasertib + crizotinib

**Darovasertib + crizotinib** is an oral combination therapy under active clinical development for the treatment of metastatic uveal melanoma (MUM) and certain solid tumors with activating GNAQ/GNA11 mutations or PKC fusions. Darovasertib is a small molecule inhibitor of protein kinase C (PKC) isoforms (conventional α, β and novel δ, ε, η, θ), while crizotinib is a small molecule inhibitor primarily targeting the c-Met receptor tyrosine kinase (also known as hepatocyte growth factor receptor, HGFR). This combination targets parallel signaling pathways (PKC/MAPK and PI3K/AKT) implicated in the growth and survival of uveal melanoma, aiming to overcome resistance associated with monotherapy. The regimen has demonstrated a high rate of tumor response and manageable safety in Phase 2 clinical trials in first-line and pretreated MUM. Darovasertib is developed by IDEAYA Biosciences, and crizotinib is marketed by Pfizer.

Brand names

Xalkori (crizotinib component)

Other names

darovasertib and crizotinib