At the American Society of Clinical Oncology (ASCO) Annual Meeting 2026, held on 29 May – 2 June, primary results from the global, multi-centre, open-label, Phase II/III OptimUM-02 clinical trial were presented. This trial evaluated the safety and efficacy of Ideaya Biosciences’ darovasertib, a first-in-class selective protein kinase C inhibitor, in combination with Pfizer’s Xalkori (crizotinib), a multi-kinase inhibitor targeting mesenchymal epithelial transition factor (MET), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), as first-line therapy in HLA A*02:01-negative metastatic uveal melanoma (UM).
In OptimUM-02, the efficacy population included 313 patients, with 210 receiving darovasertib plus Xalkori and 103 receiving investigator’s choice therapy. The combination met the primary efficacy endpoint, improving median progression-free survival by blinded independent central review to 6.9 months versus 3.1 months with investigator’s choice therapy(hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.30–0.59; p<0.0001), reducing the risk of progression or death by 58%. Darovasertib plus Xalkori also delivered a substantially higher objective response rate of 37.1% versus 5.8%, including five complete responses, while disease control rate improved to 73.3% versus 31.1%. Median duration of response was 6.8 months with the combination and was not evaluable in the control arm.
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Overall survival data remains immature, although an early favourable trend was observed. Treatment-related adverse events (TRAEs) occurred in 98.3% of patients receiving darovasertib plus Xalkori versus 89.0% with investigator’s choice therapy, while Grade 3 or 4 TRAEs were broadly similar at 40.6% versus 37.0%. Importantly, serious TRAEs were lower with darovasertib plus Xalkori than with investigator’s choice therapy, at 9.2% versus 25.0%. Discontinuations due to TRAEs were also lower for darovasertib and Xalkori, at 2.5% and 10.0%, respectively, compared with 19.0% for investigator’s choice therapy. These results support darovasertib plus Xalkori as a potential new standard of care if approved for HLA A*02:01-negative metastatic UM.
The combination of darovasertib plus Xalkori has a differentiated competitive position because there are currently no direct approved or late-stage competitors specifically targeting first-line HLA A*02:01 negative metastatic UM. Immunocore’s Kimmtrak (tebentafusp) remains the only approved systemic therapy with a proven survival benefit in metastatic UM, but its use is restricted to HLA A*02:01-positive patients, leaving the HLA A*02:01-negative population underserved.
DelcathSystems’ Hepzato (melphalan hydrochloride) is a liver directed melphalan delivery system for selected patients with unresectable hepatic metastases, making it complementary rather than a direct systemic competitor. The closest pipeline challenger is Replimune’s sturlimogene erparepvec plus Bristol Myers Squibb’s (BMS’s) Opdivo (nivolumab), which is being tested in a randomized Phase II/III REVEAL study against BMS’s Yervoy (ipilimumab) plus Opdivo in immune checkpoint inhibitor-naive metastatic UM irrespective of HLA status.
According to GlobalData’s analyst consensus forecast, global sales of darovasertib are expected to reach $709m by 2032. The planned NDA submission in the second half of 2026 could position Ideaya to capture a US opportunity, while Servier’s ex-US rights provide a broader commercial pathway across international markets.
Despite the positive OptimUM-02 readout, darovasertib’s commercial upside may be limited by the small size of the metastatic uveal melanoma market, meaning Ideaya will likely need successful expansion into earlier treatment settings, particularly neoadjuvant primary uveal melanoma, to support stronger long-term revenue growth.
