Ideaya Biosciences presents clinical data from OptimUM-09 trial

Ideaya Biosciences (IDYA) presented clinical data from their ongoing Phase 2 OptimUM-09 trial of neoadjuvant darovasertib in patients with primary uveal melanoma. The data were presented at the 2025 European Society of Medical Oncology in Berlin, Germany. There are currently no approved systemic therapies for patients with primary UM, and there is a critical unmet need for new treatment options that reduce the risk of eye removal and vision loss and have the potential to delay or prevent progression to metastatic disease. Data presented at ESMO were from a total of 95 primary UM patients, including 56 patients recommended for EN and 39 patients eligible for PB as of a data cut-off date of June 13. Patients were enrolled into Cohort 1 or Cohort 2 based on investigator recommended primary local therapy at baseline, as determined by tumor size and proximity to critical eye structures. Patients received neoadjuvant darovasertib for up to 12 cycles prior to definitive primary local therapy. As of the cut-off date, only 94 patients were evaluable for efficacy, which reflects one patient in Cohort 2 that was excluded per protocol based on not yet receiving at least one dose of study drug and at least one post-baseline tumor assessment. Patients who derive benefit from darovasertib in the neoadjuvant setting are then eligible to receive up to six additional cycles of darovasertib as adjuvant therapy and will be monitored for disease recurrence and changes in visual acuity. Tumor shrinkage and eye preservation. Patients recommended for EN demonstrated robust ocular tumor shrinkage following treatment with darovasertib, with approximately 84% experiencing any reduction in tumor size by product of diameters, and 50% and 37.5% achieving a greater than or equal to 20% and greater than or equal to 30% reduction, respectively. Similarly, among patients eligible for PB approximately 82% achieved any reduction in ocular tumor size by product of diameters, with 60.5% and 44.7% achieving a greater than or equal to 20% and greater than or equal to 30% reduction, respectively. Among 42 patients in Cohort 1 who had completed primary local therapy at the time of the data cut, a 57.1% eye preservation rate was observed. Of these patients, 75% received PB and 25% received external beam radiation instead of the EN procedure. Among patients in Cohort 1 with greater than or equal to20% tumor shrinkage prior to primary local therapy, the eye preservation rate jumped to 95%. Based in part on these data, and after discussions with the FDA, the company has proposed greater than or equal to20% tumor shrinkage as the definition of response in primary UM for their ongoing Phase 3 trial of darovasertib in the neoadjuvant setting. Predicted radiation reduction and visual preservation. Among 37 evaluable patients with paired dosimetry in Cohort 2, approximately 70% observed any reduction in the predicted dose of radiation to critical eye structures compared to baseline following treatment with darovasertib in the neoadjuvant setting, with approximately 35%-40% experiencing a greater than or equal to 20% reduction. This magnitude of reduction is relevant since a similar decrease in radiation to the tumor apex is associated with improved visual outcomes. Overall, 64.9% of the evaluable patients in Cohort 2 had a reduced predicted risk of vision loss at 3-years post-PB based on a vision prognostic tool developed at the Cleveland Clinic that is used to predict the risk of developing 20/200 vision or worse following radiation administered during PB. Improved visual acuity during neoadjuvant treatment Overall, 54.7% of patients in Cohort 1 and 60.5% of patients in Cohort 2 demonstrated an improvement in visual acuity scores during neoadjuvant darovasertib therapy, compared to baseline. Patients in Cohort 1 with improved VAS scores from baseline had a mean gain of 17 letters while on treatment, with 72% gaining greater than or equal to 5 letters at 2 consecutive visits. Similarly, patients in Cohort 2 with improved VAS scores from baseline had a mean gain of 10 letters while on treatment, with 52% gaining greater than or equal to 5 letters at 2 consecutive visits. Darovasertib was generally well tolerated with manageable adverse events, which included low-grade diarrhea, nausea, vomiting, and fatigue. Grade 3 or higher treatment related adverse events occurred in 16.8% of patients. Rates of treatment-related serious adverse events and treatment discontinuation due to adverse events were low. Ideaya is conducting a Phase 3 trial of darovasertib as a single-agent in the neoadjuvant setting of primary UM. The company is also targeting to report topline median progression free survival data from its registration-enabling Phase 2/3 trial evaluating darovasertib in combination with crizotinib in first-line, HLA*A2:01-negative metastatic UM by the end of 2025 to Q1’26 to enable a potential accelerated approval filing in the United States.