FDA Grants Breakthrough Therapy Designation to Darovasertib in Melanoma

US FDA

• The FDA has granted breakthrough therapy designation (BTD) to darovasertib as a neoadjuvant treatment for adult patients with primary uveal melanoma.
• Darovasertib is a potential first-in-class protein kinase C (PKC) inhibitor.
• Updated findings from a phase 2 trial (NCT05907954) evaluating neoadjuvant darovasertib for patients with uveal melanoma support this BTD.

The FDA has granted darovasertib, a potential first-in-class PKC inhibitor, BTD for the potential treatment of adult patients with primary uveal melanoma for whom enucleation has been recommended.¹

Updated interim data from an ongoing, open-label, phase 2 trial of neoadjuvant darovasertib given as a monotherapy for patients with localized uveal melanoma support this designation. Findings reported in September 2024 showed an 82% ocular tumor shrinkage rate and a 61% eye preservation rate in patients with uveal melanoma.

Additional data on efficacy, safety, radiation reduction, eye preservation, and vision preservation and improvement on treatment in neoadjuvant uveal melanoma were submitted as part of the BTD application. According to the press release from IDEAYA Biosciences, Inc., these findings are expected to be presented at medical conferences in 2025.

"We are pleased to receive FDA breakthrough therapy designation as we prepare to advance neoadjuvant darovasertib into a potential phase 3 registrational trial in patients with primary [uveal melanoma]. This designation highlights the potential of monotherapy darovasertib in a patient population with significant unmet medical need where there are currently no FDA-approved systemic therapies," said Darrin Beaupre, MD, PhD, chief medical officer of IDEAYA Biosciences, in a press release.

This BTD designation follows an FDA fast track designation granted to the combination of darovasertib with crizotinib (Xalkori) in December 2022 for the potential treatment of adult patients with metastatic uveal melanoma², and an orphan drug designation from the FDA in May 2022.³

A phase 2/3 registration-enabling trial (NCT05987332) is currently ongoing, evaluating the combination of darovasertib and crizotinib for the first-line treatment of patients with HLA-A2-negative metastatic uveal melanoma.¹

A randomized, registrational, phase 3 trial plans to further assess neoadjuvant darovasertib in this patient population.¹ The study plans to initiate in the first half of 2025. The study aims to evaluate neoadjuvant darovasertib in primary patients with uveal melanoma who are eligible for enucleation (cohort 1) or plaque brachytherapy (cohort 2).

"We are targeting to present the updated phase 2 clinical data in neoadjuvant [uveal melanoma] that was provided as part of the BTD application at multiple medical conferences in 2025," added Yujiro S. Hata, president and chief executive officer of IDEAYA Biosciences, in the press release.

References

1. IDEAYA Biosciences receives US FDA breakthrough therapy designation for darovasertib monotherapy in neoadjuvant uveal melanoma. News release.IDEAYA Biosciences, Inc. March 31, 2025. Accessed March 31, 2025. https://tinyurl.com/hfvdvcmr

2. IDEAYA Biosciences receives fast track designation for darovasertib combination therapy with crizotinib for the treatment of metastatic uveal melanoma. News release. IDEAYA Biosciences, Inc. December 5, 2022. Accessed March 31, 2025. https://tinyurl.com/4d7jefud

3. IDEAYA Biosciences receives orphan drug designation for darovasertib, a PKC inhibitor, for the treatment of uveal melanoma. News release. IDEAYA Biosciences. May 02, 2022. Accessed March 31, 2025. https://bit.ly/3kzf33A