Positive phase 2 data for neoadjuvant darovasertib offers hope for unmet need in uveal melanoma

Positive results from the ongoing Phase 2 OptimUM-09 trial are encouraging for the treatment of uveal melanoma (UM). According to the press release from IDEAYA Biosciences, the developers of this therapeutic candidate, “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.”¹

The data presented were from 2 cohorts of patients. The first cohort included 56 patients who were recommended for enucleation (EN). The second cohort included 39 patients who were eligible for plaque brachytherapy (PB).

In cohort 1 (EN) the data showed “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.”¹ In 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.”¹

Patients in cohort 1 who had completed primary local therapy had an eye preservation rate of 57.1% (24/42) at the time of the data cut.¹ The eye preservation rate increased to 95% (19/20) for patients in cohort 1 that has tumor shrinkage of ≥20%.¹

Cohort 2 has 37 eligible patients with paired dosimetry. Of these patients, 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.”¹

A reported “54.7% (29/53) patients in cohort 1 and 60.5% (23/38) of patients in cohort 2”¹ saw an improvement in visual acuity scores when compared to their baseline scores. Cohort 1 saw a mean gain of 17 letters while on treatment. Cohort 2 saw a mean gain of 10 letters while on treatment.¹

The safety and tolerability of the darovasertib noted that the treatment was “well tolerated with manageable adverse events.”¹ Additionally, treatment-related adverse events that were of a grade 3 or higher occurred in 16.8% (16/95) of patients. Treatment-related serious adverse events were reported at a rate of 5.3%.¹

Based on these positive results, a Phase 3 trial, OptimUM-10, will evaluate “darovasertib as a single-agent in the neoadjuvant setting of primary UM.”¹ 

Reference:

1. IDEAYA Biosciences Announces Positive Phase 2 Data for Darovasertib in the Neoadjuvant Setting of Primary Uveal Melanoma in a Proffered Paper Oral Presentation at ESMO 2025. IDEAYA Biosciences, Inc. News release. October 20, 2025. Accessed October 28, 2025. https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-positive-phase-2-data-for-darovasertib-in-the-neoadjuvant-setting-of-primary-uveal-melanoma-in-a-proffered-paper-oral-presentation-at-esmo-2025-302588310.html