Breakthrough Clinical Results
IDEAYA Biosciences announced that data from a Phase 2 clinical trial of neoadjuvant darovasertib in primary uveal melanoma will be presented at the 2025 European Society for Medical Oncology (ESMO) meeting. The trial included over 90 patients in both plaque brachytherapy and enucleation-eligible cohorts. Darovasertib has received FDA Breakthrough Therapy Designation for use in neoadjuvant uveal melanoma in patients requiring enucleation. A Phase 3 neoadjuvant registrational trial (OptimUM-10) has also been initiated.
Key Highlights
- Positive Phase 2 data on neoadjuvant darovasertib in primary uveal melanoma accepted for oral presentation at ESMO 2025.
- Data includes over 90 patients across plaque brachytherapy and enucleation cohorts.
- Darovasertib has received FDA Breakthrough Therapy Designation for this indication.
- Phase 3 neoadjuvant registrational trial (OptimUM-10) initiated.
Incidence and Prevalence
Global Incidence and Prevalence of Uveal Melanoma
Uveal melanoma is the most common primary intraocular malignancy in adults. Despite its rarity, this cancer carries a high mortality rate with approximately 50% of patients dying of metastases.
Global Incidence Patterns
According to the most recent data from 2021, the mean age-adjusted incidence of uveal melanoma is 5.1 per million (95% CI 4.2-6.1). The incidence shows significant geographical variation:
- ≥8.0 cases per million person-years in Northern Europe, Western Europe, and Oceania
- 2.0 to 7.9 cases per million person-years in North America, Eastern Europe, and Southern Europe
- <2.0 cases per million person-years in South America, Asia, and Africa
In Europe, uveal melanoma has an incidence rate of up to 1.0 per 100,000 persons per year (equivalent to 10 per million).
Demographic Patterns
The disease demonstrates clear demographic patterns:
- Higher incidence in males (5.9 per million, CI=4.4-7.6) compared to females (4.5 per million, CI=3.3-5.8), P<0.001
- Most commonly occurs in the sixth decade of life (mean age 61.4±15 years)
- Predominantly affects Caucasians (94.7% of cases)
- Highest in populations of European ancestry and lowest in populations of Asian and African ancestry
Geographic Distribution
In the United States, a large nationwide cohort study analyzing 277,120 histologically confirmed melanoma patients between 1973 and 2012 found that uveal melanoma represented 3.2% of all recorded cases of melanoma (7,516 cases). 52.3% of cases were reported in the Western US (with 35.7% in California specifically).
Incidence Trends
Overall incidence trends are stable for most countries (28/35 countries studied). Interestingly, uveal melanoma incidence correlates with latitude (r = 0.77, P ≤ 0.001) and is expressed as a north-to-south decreasing gradient in Europe.
Survival and Metastasis
The 5-year relative survival rates for uveal melanoma are 79.8%±5.8% (overall) and 76%±5.3% (cancer-specific). The mean 5-year cancer-specific survival rate (76%) remained stable during the study period between 1973 and 2012.
Metastatic uveal melanoma develops in 6.5-35% of patients, most commonly to the liver. The median time for metastases development is 25.63 months (range: 0.17-102.43 months).
Risk Factors
Epidemiological risk factors include light iris color and specific single-nucleotide-polymorphisms (SNPs). The SNP rs12913832 correlates with ocular melanoma incidence (r = 0.83, P ≤ 0.001).
Treatment Trends
Treatment patterns have evolved significantly, with the percentage of uveal melanoma cases managed by surgery alone decreasing by 69.4% between 1973-1977 and 2006-2012, with a concomitant 62% increase in primary radiotherapy. Radiotherapy has shown significantly improved survival compared to surgery alone (15.4±0.4 vs 13.6±0.3, P<0.001).
Drug used in other indications
Darovasertib Clinical Trials Beyond Uveal Melanoma
Based on the available information, there are no documented clinical trials of Darovasertib for indications other than uveal melanoma. The only clinical application mentioned in the available data is the use of Darovasertib in combination with crizotinib for treating uveal melanoma.
In the documented case, Darovasertib was used as a neoadjuvant treatment in combination with crizotinib for a patient with a large uveal melanoma in their only functional eye. This combination therapy demonstrated significant efficacy, with the tumor showing substantial regression after 6 months of treatment: - The tumor decreased from 18 mm in maximal diameter to 14.1 mm - Tumor thickness reduced from 16.5 mm to just 2.6 mm
This remarkable regression allowed the medical team to proceed with plaque brachytherapy rather than having to perform a more invasive enucleation procedure.
The researchers concluded that this combination of darovasertib and crizotinib represents an effective neoadjuvant strategy for uveal melanoma that warrants further investigation.
However, there is no information available regarding: - Clinical trials of Darovasertib for other disease indications - Intervention models for trials in other conditions - Alternative dosing regimens or administration protocols - Other combination therapy approaches with Darovasertib
The current research focus appears to be exclusively on Darovasertib's application in uveal melanoma treatment, particularly in the neoadjuvant setting when combined with crizotinib.
IDEAYA Biosciences, Inc. Drug Approvals in the Last Three Years
Based on a comprehensive review of IDEAYA Biosciences, Inc.'s portfolio, there is no evidence of any FDA-approved drugs or therapies that have received regulatory authorization for any indications within the past three years (2021-2024).
IDEAYA Biosciences is a precision medicine oncology company that focuses on developing targeted therapeutics for specific patient populations. The company has been advancing several clinical-stage candidates through its pipeline, particularly in the areas of synthetic lethality and precision medicine oncology.
Their most advanced programs include:
- IDE397: A MAT2A inhibitor being investigated for tumors with MTAP deletion
- Darovasertib (IDE196): A PKC inhibitor being studied for metastatic uveal melanoma and other solid tumors
- IDE161: A PARG inhibitor for tumors with HRD mutations
While these programs have shown promising clinical data in various phase 1 and phase 2 trials, none have yet received full regulatory approval for commercial use in any therapeutic indication.
The company continues to advance its development pipeline and has established several strategic partnerships with larger pharmaceutical companies to help bring their innovative therapies to market. However, as of current information, IDEAYA Biosciences remains a clinical-stage biopharmaceutical company without approved products on the market.
Investors and patients interested in IDEAYA's progress should monitor upcoming clinical trial results and regulatory submissions that may lead to potential approvals in the future as their candidates progress through late-stage clinical development.