Neoadjuvant Darovasertib in Primary Uveal Melanoma

Phase 3

Not yet recruiting

• Conditions: Uveal Melanoma
• Interventions: Drug: Darovasertib; Procedure: Primary Local Therapy

• Registration Number: NCT07015190
• Lead Sponsor: IDEAYA Biosciences

Brief Summary

This is a Phase 3, randomized, multi-center, open-label study of neoadjuvant darovasertib in subjects with primary non-metastatic uveal melanoma

Detailed Description

The study is divided into 2 cohorts of patients with primary uveal melanoma requiring either plaque brachytherapy or enucleation.

In cohort 1, patients in the treatment arm will receive neoadjuvant darovasertib followed by plaque brachytherapy compared to immediate plaque brachytherapy (control arm).

In cohort 2, the treatment arm will receive neoadjuvant darovasertib followed by definitive primary local therapy (i.e., plaque brachytherapy, proton beam radiation, or enucleation). Subjects in the control arm will go onto immediate enucleation.

Subjects will then receive primary local therapy following neoadjuvant darovasertib.

All patients will be followed for up to 3 years to assess longer term outcomes such as vision and tumor recurrence.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-03
• Study First Submitted QC: 2025-06-03
• Study First Posted: 2025-06-11
• Last Update Submitted: 2025-06-20
• Last Update Posted: 2025-06-25
• Study Start: 2025-09-30
• Primary Completion: 2027-05-07
• Study Completion: 2027-12-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 520

Inclusion Criteria

• Primary non-metastatic uveal melanoma
• Able and willing to provide written, informed consent before initiation of any study-related procedures, and in the opinion of the Investigator, to comply with all study requirements
• ECOG 0 or 1
• Adequate organ function

Exclusion Criteria

• Previous treatment for UM
• Evidence of metastatic UM
• Attributes that necessitate enucleation regardless of response to therapy
• Evidence of progressive secondary underlying ocular disease that would confound longitudinal VA assessments
• Presence of a malignant disease other than the one being treated in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Darovasertib	Darovasetib followed by definitive primary local therapy (i.e., PB, proton beam radiation, or enucleation)
Control Arm	Primary Local Therapy	Immediate Primary Local therapy

Primary Outcome Measures

Name	Time	Method
Cohort 1: To demonstrate that the proportion of subjects with vision loss is lower for subjects in the Treatment Arm vs the Control Arm	Approximately 3 years	Loss of Best Corrected Visual Acuity (BCVA) of ≥ 15 letters using Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA
Cohort 2: To demonstrate the ability to salvage the eye and prevent enucleation in the Treatment Arm	Approximately 2 years	Eye preservation rate