IDEAYA Completes Pivotal Trial Enrollment for Uveal Melanoma Drug

SOUTH SAN FRANCISCO, CA – December 11, 2025 – IDEAYA Biosciences has reached a critical milestone in its quest to bring a new therapy to patients with a rare and aggressive eye cancer, announcing the completion of enrollment in its registration-enabling Phase 2/3 trial. The study, known as OptimUM-02, is evaluating the company's investigational drug, darovasertib, in combination with Pfizer’s crizotinib for a specific subgroup of patients with metastatic uveal melanoma (mUM).

The successful enrollment of 435 patients paves the way for the next major catalyst: the release of topline data. IDEAYA anticipates reporting median progression-free survival (PFS) results in the first quarter of 2026, which it plans to use for a potential accelerated approval filing with the U.S. Food and Drug Administration (FDA). This achievement marks a significant step forward for the precision oncology company and offers a beacon of hope for a patient population with historically grim prospects.

A New Front in a Forgotten Cancer

Metastatic uveal melanoma is the most common primary eye cancer in adults, yet it remains a rare disease, affecting approximately 7,000 people globally each year. Despite its rarity, its prognosis is severe. Once the cancer spreads from the eye, typically to the liver, about 50% of patients will not survive beyond one year. For decades, this patient community faced a desolate treatment landscape with no approved therapies and little benefit from traditional chemotherapies or even the immunotherapies that revolutionized cutaneous (skin) melanoma treatment.

This landscape began to change in 2022 with the approval of Immunocore’s Kimmtrak (tebentafusp). However, Kimmtrak’s efficacy is limited to a specific genetic subgroup: patients who are HLA-A*02:01-positive, which accounts for roughly 40-50% of the Caucasian population where uveal melanoma is most prevalent. This created a stark divide in care, leaving the other half of patients—the HLA*A2-negative population—without a dedicated, FDA-approved first-line treatment.

It is precisely this unmet need that IDEAYA aims to fill. The OptimUM-02 trial exclusively enrolls first-line HLA*A2-negative patients, positioning the darovasertib-crizotinib combination as a potential standard of care for this underserved group.

"We are very pleased to announce that we have achieved the target enrollment to enable potential full approval filing in our Phase 2/3 registration-enabling trial," said Yujiro S. Hata, President and CEO of IDEAYA Biosciences, in the company's official statement. He highlighted the "clear unmet need" and "strong clinical interest" as drivers of the rapid enrollment, pointing to the combination's potential to "meaningfully impact patients with this devastating disease."

Promising Data in a Segmented Market

IDEAYA's strategy hinges on a combination therapy targeting two key cancer pathways. Darovasertib is a protein kinase C (PKC) inhibitor, designed to block a pathway activated by GNAQ and GNA11 gene mutations, which are present in over 90% of uveal melanoma cases. It is combined with crizotinib, a c-MET inhibitor, which targets a separate pathway implicated in tumor growth and resistance.

Early data from a smaller Phase 1/2 study, OptimUM-01, has been highly encouraging. Results presented in late 2025 showed the combination achieved a median Overall Survival (OS) of 21.1 months and a median Progression-Free Survival (PFS) of 7.0 months in first-line patients.

When placed in the context of the current market, these figures are compelling. Kimmtrak, the approved therapy for HLA-A*02:01-positive patients, demonstrated a median OS of 21.7 months in its pivotal trial—a figure remarkably similar to the preliminary data for IDEAYA's combination. However, the key differentiator may be PFS. Kimmtrak's median PFS was 3.3 months, less than half the 7.0 months observed for the darovasertib combination. If the larger OptimUM-02 trial confirms this superior PFS, it would represent a significant clinical advantage in delaying disease progression.

For the HLA*A2-negative patients in the OptimUM-02 trial, the control arm consists of the investigator's choice of therapy, including immunotherapies like pembrolizumab or ipilimumab plus nivolumab. These treatments have shown limited efficacy in uveal melanoma, setting a relatively low bar for the darovasertib-crizotinib combination to demonstrate superiority.

A De-Risked Path to Market

Beyond the promising clinical data, IDEAYA has strategically navigated the regulatory landscape to accelerate darovasertib’s path to market. The program has garnered a trifecta of valuable FDA designations: Fast Track, Breakthrough Therapy, and Orphan Drug.

• Fast Track Designation for the combination in metastatic UM facilitates more frequent communication with the FDA and allows for a "rolling review," where the company can submit sections of its New Drug Application (NDA) as they are completed, potentially shortening the review timeline.
• Breakthrough Therapy Designation for darovasertib as a single agent in an earlier, neoadjuvant setting provides intensive FDA guidance and further validates the drug's potential for substantial improvement over existing therapies.
• Orphan Drug Designation for uveal melanoma provides powerful incentives, including a potential seven years of market exclusivity upon approval and exemption from certain costly regulatory fees.

Together, these designations create a highly favorable regulatory environment. The ability to file for accelerated approval based on the PFS endpoint from OptimUM-02 could allow the drug to reach patients sooner, while the company collects the longer-term Overall Survival data required for a full approval. This dual-endpoint strategy effectively de-risks the final stages of development and shortens the timeline to potential revenue generation.

The collaboration with Pfizer, which supplies crizotinib for the trial, also lends significant credibility and stability to the program. While the exact financial terms are not public, the partnership ensures a reliable supply of a key component of the therapy and signals confidence from a major pharmaceutical player. Should the data prove positive, the two companies will negotiate a path forward for regulatory submission and commercialization, a crucial step in bringing the combination therapy to the global market. With an estimated addressable population of several thousand new patients each year in the HLA*A2-negative segment, the commercial opportunity is substantial for a therapy that could become the first-line standard of care. All eyes will now be on the first quarter of 2026, when the next data readout will determine if this new hope for uveal melanoma patients becomes a clinical reality.