(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma

Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma

Study Overview

• Status: Active, not recruiting
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: Darovasertib

Detailed Description

Phase 2 multi-center open-label IDE196 study in patients with primary uveal melanoma (UM) requiring either enucleation or plaque brachytherapy. Patients will be treated in neoadjuvant setting up to 12 months (or maximum benefit) followed by primary local therapy. An additional 6 months of adjuvant treatment may be given to some patients. All patients will have long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Health Sydney
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Centre
• France
  • Paris, France, 75005
    • Institute Curie
• Germany
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Institute
  • Florida
    • Miami, Florida, United States, 33146
      • University of Miami
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • The Cancer and Hematology Centers
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Primary localized uveal melanoma requiring either enucleation or plaque brachytherapy
• Cohort 3 (patients with small UM tumors) - clinically diagnosed uveal (not iris) melanoma that is < 4 mm in thickness requiring treatment
• Able to dose orally
• ECOG Performance status of 0-1
• No other significant underlying ocular disease
• Adequate organ function
• Not pregnant/nursing or planning to become pregnant. Willing to use birth control

Exclusion Criteria:

• Previous treatment with a Protein Kinase C (PKC) inhibitor
• Concurrent malignant disease
• Active HIV infection or Hep B/C
• Malabsorption disorder
• Unable to discontinue prohibited medication
• Impaired cardiac function or clinically significant cardiac disease
• Any other condition which may interfere with study interpretation or results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: darovasertib; IDE196 (darovasertib) oral open label	Drug: Darovasertib; Oral, potent, selective inhibitor of Protein Kinase C; Other Names: IDE196; LXS196

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and significant laboratory abnormalities	Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs. Lab results will be summarized by change from baseline values, frequency of newly occurring on-treatment Grade 3 or 4 events; worst on-treatment value compared to baseline.	from first dose to 28 days after last dose of therapy, approximately 18 months
Cohort 1 (enucleation): Number of patients converted from requiring enucleation to radiation	Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months
Cohort 2 (plaque brachytherapy): Estimated change in modeled radiation dose	Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months
Cohort 3 (patients with small UM tumors): Number of patients with clinical benefit per protocol-defined UM response criteria	Proportion of patients with clinical benefit rate (CBR) defined as complete response (CR) + partial response (PR) + stable disease (SD) for ≥ 12 weeks per UM response criteria	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of visual acuity loss	Best corrected visual acuity loss over time	from time of primary local therapy to one year after surgery, approximately 12 months
Rate of local disease recurrence	Evaluate uveal melanoma progression or recurrence	from date of primary local therapy to end of follow-up, approximately 36 months
Evaluate tumor response to neoadjuvant IDE196	Measurement of tumor diameter and thickness before and after neoadjuvant therapy with IDE196, specifically as measured by ocular ultrasound, evaluating largest basal diameter and apical thickness of the uveal melanoma (measured in millimeters)	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months
Cohort 3 (patients with small UM tumors): Effect of neoadjuvant IDE196 therapy on the natural history of small UM tumors	Time from first dose of neoadjuvant to primary local therapy	from first dose of neoadjuvant to primary local therapy, approximately 12 months
Cohort 3 (patients with small UM tumors): Efficacy of neoadjuvant IDE196 therapy on small UM tumors	Tumor response (complete response and partial response) as measured by protocol-defined UM response criteria	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of metastatic disease	Evaluate occurrence of metastatic uveal melanoma	from date of primary local therapy to end of follow-up, approximately 36 months
Overall survival	Evaluate patient survival status	from date of first dose to end of follow-up, approximately 54 months

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences
• Investigators: Study Director: Jasgit Sachdev, MD, IDEAYA Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Brachytherapy; Neoadjuvant; Adjuvant; Uveal Melanoma; Plaque; Ophthalmology; Ocular Oncology; Ocular melanoma; Enucleation; Protein Kinase C; Plaque brachytherapy; Darovasertib; IDE196; Choroid melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Neoplasms by Histologic Type; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Uveal Diseases; Melanoma; Pathological Conditions, Signs and Symptoms; Uveal Neoplasms; Plaque, Amyloid; Uveal Melanoma
• Other Study ID Numbers: IDE196-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No