Focusing on the future of uveal melanoma treatment
UM—the most common ocular cancer—has a high risk of metastatic progression and poor long-term survival. Biologically and clinically distinct from cutaneous melanomas, it typically shows limited responses to standard melanoma therapies.1,3-5
~2500
to 3500
people in the US are diagnosed with uveal melanoma each year.4,6
Currently, a significant need for novel, targeted therapies exists in UM1,2
For primary UM
While current therapies provide local tumor control, they are associated with a risk of vision loss or loss of the eye itself1
For metastatic UM
Only 1 FDA-approved systemic therapy exists, which is restricted to the HLA-A*02 positive population2,4
Darovasertib: a first-in-class, oral, targeted protein kinase C (PKC) inhibitor under investigation in primary and metastatic UM
Darovasertib was designed to have unique selectivity for the PKC isoforms (PKCδ/ε), which are downstream of the GNAQ/11 driver mutations that are responsible for UM tumor initiation and progression in nearly all cases of UM.2
In preclinical studies, darovasertib demonstrated:
Effective inhibition of oncogenic PKC pathway activation2
Consistent UM antitumor activity in both in vitro cellular models and in vivo xenograft system5
cMET overexpression and pathway overactivation is associated with UM tumor metastasis, suggesting that adding a cMET inhibitor such as crizotinib to darovasertib may enhance efficacy in the metastatic setting.2,7
*Pfizer's oral cMET inhibitor.
The OptimUM Trials: investigating outcomes for patients with UM
OptimUM is a series of trials investigating the use of darovasertib in the primary and metastatic settings for UM.
TRIAL INFORMATION | POPULATION | PHASE 1 P1 | PHASE 2 P2 | PHASE 3 P3 | STATUS |
|---|---|---|---|---|---|
OptimUM-01 (darovasertib ± crizotinib)8 Patients with metastatic UM and other solid tumors harboring GNAQ/11 mutations or PKC fusions Currently active but not enrolling | Patients with metastatic UM and other solid tumors harboring GNAQ/11 mutations or PKC fusions | Currently active but not enrolling | |||
OptimUM-02 (darovasertib + crizotinib)9 Registration trial in patients with HLA-A*02:01 negative metastatic UM Currently active but not enrolling | Registration trial in patients with HLA-A*02:01 | Currently active but not enrolling | |||
OptimUM-09 (darovasertib)10 Patients with primary nonmetastatic UM requiring either enucleation or plaque brachytherapy in the neoadjuvant setting Currently active but not enrolling | Patients with primary nonmetastatic UM requiring either enucleation or plaque brachytherapy in the neoadjuvant setting | Currently active but not enrolling | |||
OptimUM-10 (darovasertib)11 Registration trial in patients with primary nonmetastatic UM requiring either enucleation or plaque brachytherapy in the neoadjuvant setting Currently open for enrollment | Registration trial in patients with primary nonmetastatic UM requiring either enucleation or plaque brachytherapy in the neoadjuvant setting | Currently open for enrollment | |||
OptimUM-11 (darovasertib + crizotinib)12 Registration trial in patients in the adjuvant setting with nonmetastatic UM who have completed primary local therapy and who are at high risk for recurrence Initiating in 2026 | Registration trial in patients in the adjuvant setting with nonmetastatic UM who have completed primary local therapy and who are at high risk for recurrence | Initiating in 2026 | |||
cMET, cellular mesenchymal-epithelial transition factor; HLA, human leukocyte antigen; HLA-A*02:01, human leukocyte antigen A02:01 major histocompatibility complex class I allele.; P1, phase 1; P2, phase 2; P3, phase 3.
Contact IDEAYA Clinical Trials to learn more.
Get in TouchDarovasertib is an investigational product and has not been approved by the U.S. Food and Drug Administration for safety or effectiveness.
References: 1. Gelmi MC, Jager MJ. Uveal melanoma: current evidence on prognosis, treatment and potential developments. Asia Pac J Ophthalmol (Phila). 2024;13(2):100060. doi:10.1016/j.apjo.2024.100060 2. Cao L, Chen S, Sun R, et al. Darovasertib, a novel treatment for metastatic uveal melanoma. Front Pharmacol. 2023;14:1232787. doi:10.3389/fphar.2023.1232787 3. Rantala ES, Hernberg MM, Piperno-Neumann S, Grossniklaus HE, Kivelä TT. Metastatic uveal melanoma: the final frontier. Prog Retin Eye Res. 2022;90:101041. doi:10.1016/j.preteyeres.2022.101041 4. Wespiser M, Neidhardt E, Negrier S. Uveal melanoma: in the era of new treatments. Cancer Treat Rev. 2023;119:102599. doi:10.1016/j.ctrv.2023.102599 5. Arang N, Lubrano S, Ceribelli M, et al. High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma. Cell Rep Med. 2023;4(11):101244. 6. American Cancer Society. Explore cancer statistics: 2026 estimated new cancer cases. Accessed January 14, 2026. https://cancerstatisticscenter.cancer.org/ 7. Machiraju D, Hassel JC. Targeting the cMET pathway to enhance immunotherapeutic approaches for mUM patients. Front Oncol. 2023;12:1068029. 8. Study of IDE196 in patients with solid tumors harboring GNAQ/11 mutations or PRKC fusions. ClinicalTrials.gov identifier: NCT03947385. Updated November 13, 2024. Accessed January 14, 2026. https://clinicaltrials.gov/study/NCT03947385 9. IDE196 (Darovasertib) in combination with crizotinib as first-line therapy in metastatic uveal melanoma. ClinicalTrials.gov identifier: NCT05987332. Updated November 7, 2025. Accessed January 14, 2026. https://clinicaltrials.gov/study/NCT05987332 10. (Neo)adjuvant IDE196 (darovasertib) in patients with localized ocular melanoma. ClinicalTrials.gov identifier: NCT05907954. Updated October 22, 2025. Accessed January 14, 2026. https://www.clinicaltrials.gov/study/NCT05907954 11. Neoadjuvant darovasertib in primary uveal melanoma. ClinicalTrials.gov identifier: NCT07015190. Updated October 10, 2025. Accessed January 14, 2026. https://clinicaltrials.gov/study/NCT07015190 12. Data on file. Ideaya Biosciences, 2025.