IDEAYA Biosciences在2025年ESMO大会上展示了Darovasertib在原发性葡萄膜黑色素瘤新辅助治疗中的2期阳性数据

SOUTH SAN FRANCISCO, Calif., Oct. 20, 2025 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, today presented positive clinical data from their ongoing Phase 2 OptimUM-09 trial of neoadjuvant darovasertib in patients with primary uveal melanoma (UM). The data were presented in a Proffered Paper oral presentation by Dr. Marcus Butler, M.D., Associate Professor, Princess Margaret Cancer Center at the University of Toronto, at the 2025 European Society of Medical Oncology (ESMO) 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 (Cohort 1) and 39 patients eligible for PB (Cohort 2) as of a data cut-off date of June 13, 2025. 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 (or maximum benefit) 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. 

"We are highly encouraged by the data from OptimUM-09 demonstrating meaningful tumor shrinkage, eye preservation and reduced predicted risk of severe vision loss, and believe these results strongly support the potential for darovasertib as the first systemic therapy for the neoadjuvant treatment of primary uveal melanoma," said Darrin Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences.

"These data highlight the potential of neoadjuvant darovasertib to significantly improve the treatment paradigm for patients requiring enucleation or plaque brachytherapy in primary uveal melanoma, helping them preserve their eye and preserve their vision with a single therapy," said Marcus O. Butler, M.D., Associate Professor, Princess Margaret Cancer Center, and lead investigator on the study.

Key Findings from OptimUM-09

Tumor shrinkage and eye preservation

• Patients recommended for EN (Cohort 1) demonstrated robust ocular tumor shrinkage following treatment with darovasertib, with approximately 84% (47/56) experiencing any reduction in tumor size by product of diameters, and 50% (28/56) and 37.5% (21/56) achieving a ≥20% and ≥30% reduction, respectively.

• Similarly, among patients eligible for PB (Cohort 2) approximately 82% (31/38) achieved any reduction in ocular tumor size by product of diameters, with 60.5% (23/38) and 44.7% (17/38) achieving a ≥20% and ≥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% (24/42) eye preservation rate was observed. Of these patients, 75% (18/24) received PB and 25% (6/24) received external beam radiation instead of the EN procedure.

• Among patients in Cohort 1 with ≥20% tumor shrinkage prior to primary local therapy, the eye preservation rate jumped to 95% (19/20). Based in part on these data, and after discussions with the FDA, the company has proposed ≥20% tumor shrinkage as the definition of response in primary UM for their ongoing Phase 3 trial (OptimUM-10) of darovasertib in the neoadjuvant setting.

Predicted radiation reduction and visual preservation

• Among 37 evaluable patients with paired dosimetry in Cohort 2, approximately 70% (26/37) observed any reduction in the predicted dose of radiation to critical eye structures (fovea, disc, lens) compared to baseline following treatment with darovasertib in the neoadjuvant setting, with approximately 35-40% experiencing a ≥20% reduction. This magnitude of reduction is relevant since a similar decrease in radiation to the tumor apex is associated with improved visual outcomes (Perez et al, Int J Radiat Oncol Biol Phys. 2014; Kheir et al, Adv Radiat Oncol. 2022; Saconn et al, Int J Radiat Oncol Biol Phys. 2010; Puusaari et al, Invest Ophthalmol Vis Sci. 2004).

• 64.9% (24/37) 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 (Aziz et al; JAMA Ophthalmol. 2016) that is used to predict the risk of developing 20/200 vision (legal blindness) or worse following radiation administered during PB.

Improved visual acuity during neoadjuvant treatment

• 54.7% (29/53) of patients in Cohort 1 and 60.5% (23/38) of patients in Cohort 2 demonstrated an improvement in visual acuity scores (VAS) 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% (21/29) gaining ≥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% (12/23) gaining ≥5 letters at 2 consecutive visits.

Safety and Tolerability:

• 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 (TRAEs) occurred in 16.8% (16/95) of patients. Rates of treatment-related serious adverse events (5.3%) and treatment discontinuation due to adverse events (6.3%) were low.

IDEAYA is conducting a Phase 3 trial (OptimUM-10) 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 (OptimUM-02) 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.