IDEAYA/Servier PKC drug aces uveal melanoma trial

Servier $210 million bet on IDEAYA's uveal melanoma therapy darovasertib seems to have paid off, as the drug has hit the mark in a phase 2/3 that could form the basis of regulatory filings later this year.

The results of the OptimUM-02 study showed that a combination regimen of PKC inhibitor darovasertib with Pfizer's cMET inhibitor Xalkori (crizotinib) achieved a statistically significant improvement in median progression-free survival (PFS) compared to a control group using investigators' choice of therapy, generally immunotherapies like MSD's Keytruda (pembrolizumab) and Bristol Myers Squibb's Opdivo (nivolumab) and Yervoy (ipilimumab).

The study enrolled previously untreated patients with HLA-A*A2:01-negative metastatic uveal melanoma (mUM), in other words, a group with the eye cancer that would not be eligible for treatment with Immunocore's Kimmtrak (tebentafusp), a TCR therapy that was approved by the FDA for HLA-A*02:01-positive mUM in 2022.

Shares in IDEAYA were up 16% on the trial results, which revealed that PFE with the darovasertib regimen was 6.9 months, versus 3.1 months in the control group. The objective response rate (ORR) came in at 37.1% and 5.8%, respectively, and there was also a trend towards improved overall survival (OS) that will continue to be monitored.

IDEAYA and Servier, which also pledged up to $320 million in regulatory and commercial milestones when it licensed rights to darovasertib last September, said that OptimUM-02 is the first randomised study to show a statistically significant and "clinically meaningful" PFS benefit in this patient population.

"Metastatic uveal melanoma is an area of high unmet medical need with poor prognosis and short overall survival, and there are currently no approved therapies for HLA-A*02:01-negative mUM patients," said Dr Meredith McKean of the Sarah Cannon Research Institute, who added that the results are "potentially practice changing."

According to IDEAYA, around 95% of patients with uveal melanoma have activating mutations in GNAQ/11 GTPase proteins that drive downstream PKC signalling and tumour growth. It estimates there are around 3,000 patients in the US, with approximately half of them progressing to mUM.

The company estimates that 50% to 70% of mUM patients have the HLA-A*02:01-negative serotype, suggesting that the market for darovasertib is at least as large as that for Kimmtrak, which brought in $400 million in sales last year.

Another treatment option is Delcath Systems' Hepzato (melphalan for injection/hepatic delivery system), which was approved by the FDA in 2023 specifically for uveal melanoma patients with unresectable liver metastases, which made around $80 million in 2025.

A Reuters report citing Truist analyst Gregory Renza said peak annual revenues for darovasertib could reach $800 million.

Photo by Judy Beth Morris on Unsplash