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

Phase 2

Recruiting

• Conditions: Uveal Melanoma
• Interventions: Drug: Darovasertib

• Registration Number: NCT05907954
• Lead Sponsor: IDEAYA Biosciences

Brief Summary

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

Detailed Description

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

Study Timeline

• Study First Submitted: 2023-06-06
• Study First Submitted QC: 2023-06-14
• Study First Posted: 2023-06-18
• Study Start: 2023-07-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-28
• Primary Completion: 2026-01-31
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Primary localized uveal melanoma requiring either enucleation or plaque brachytherapy
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
darovasertib	Darovasertib	IDE196 (darovasertib) oral open label

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs) and significant laboratory abnormalities	from first dose to last dose of adjuvant therapy, approximately 12 months	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.
Cohort 1 (enucleation): Number of patients converted from requiring enucleation to radiation	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months	Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy
Cohort 2 (plaque brachytherapy): Estimated change in modeled radiation dose	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months	Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy

Secondary Outcome Measures

Name	Time	Method
Evaluate tumor response to neoadjuvant IDE196	from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 6 months	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)
Assessment of visual acuity loss	from time of primary local therapy to one year after surgery, approximately 12 months	Best corrected visual acuity loss over time
Rate of local disease recurrence	from date of primary local therapy to end of follow-up, approximately 36 months	Evaluate uveal melanoma progression or recurrence
Rate of metastatic disease	from date of primary local therapy to end of follow-up, approximately 36 months	Evaluate occurrence of metastatic uveal melanoma

Trial Locations

Locations (24)

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Moores Cancer Center; 🇺🇸 La Jolla, California, United States

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

University of Miami; 🇺🇸 Miami, Florida, United States

The Cancer and Hematology Centers; 🇺🇸 Grand Rapids, Michigan, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Northwell; 🇺🇸 Manhasset, New York, United States

Duke University Health System; 🇺🇸 Durham, North Carolina, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

St. Vincent's Health Sydney; 🇦🇺 Sydney, New South Wales, Australia

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Institute Curie; 🇫🇷 Paris, France

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

University Hospital Essen - West German Cancer Center; 🇩🇪 Essen, Germany

Fondazione IRCCS Istituto Nazionale Tumori; 🇮🇹 Milan, Italy

Instituto Nazionale Tumori IRCCS - Fondazione Pascale; 🇮🇹 Napoli, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Rome, Italy

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

University College London Hospital - NHS Foundation Trust; 🇬🇧 London, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Wirral, United Kingdom