Phase 3 darovasertib PKC inhibitor plus crizotinib c-MET/ALK inhibitor in adjuvant uveal melanoma

IDEAYA Biosciences’ OptimUM-11 is a randomized, multi-center, open-label Phase 3 study testing whether adjuvant darovasertib (IDE196; a small-molecule protein kinase C inhibitor) combined with crizotinib (a small-molecule c-MET/HGFR and ALK inhibitor; marketed as Xalkori by Pfizer) can reduce recurrence risk after definitive local therapy for primary, non-metastatic uveal melanoma. Participants are assigned to darovasertib + crizotinib versus observation/follow-up (no active anti-cancer treatment), aiming to quantify whether systemic pathway inhibition can delay or prevent metastatic progression in a disease where many patients relapse despite excellent local control. The commercial/scientific angle is bringing a PKC-centered targeted regimen—already developed in metastatic uveal melanoma—into the adjuvant setting, where event rates and follow-up duration drive registrational value. Today’s care after plaque brachytherapy, proton beam, or enucleation is surveillance imaging and liver-directed interventions only if metastases emerge; there is no established adjuvant systemic therapy that reliably prevents relapse in primary uveal melanoma.