Darovasertib before Surgery or Radiation Therapy to Treat Early-stage Eye Cancer (Uveal Melanoma)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ideaya Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

10 Apr 2026 → ongoing

Decision date (initial)

2026-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

IDEAYA Biosciences, Inc

External identifiers

EU CT number

2025-522387-32-00

ClinicalTrials.gov

NCT07015190

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Others

Cohort 1: To demonstrate that the proportion of subjects with vision loss is lower for subjects in the Treatment Arm vs the Control Arm
Cohort 2: To demonstrate the ability to salvage the eye and prevent enucleation in the Treatment Arm

Secondary objectives 10

1. Both Cohorts: To evaluate neoadjuvant darovasertib treatment with respect to objective response rate (ORR) per the UM response criteria by Blinded Independent Central Review (BICR)
2. Both Cohorts: To compare neoadjuvant darovasertib to immediate PB or enucleation with respect to EFS
3. Both Cohorts: To evaluate the safety and tolerability of darovasertib in the neoadjuvant setting
4. Both Cohorts: To evaluate neoadjuvant darovasertib treatment response per UM response criteria with respect to ORR_UM by Investigator assessment and disease control rate (DCR) by Investigator assessment and BICR
5. Both Cohorts:To evaluate BCVA improvement in the Treatment Arms relative to baseline during the neoadjuvant treatment period
6. Cohort 1: To demonstrate a reduction in the proportion of subjects with clinically significant ME in the Treatment Arm vs the Control Arm
7. Cohort 1:To assess severe VA loss for subjects in the Treatment Arm vs the Control Arm
8. Cohort 1:To evaluate the effect of neoadjuvant darovasertib treatment on the reduction of radiation dose by comparing baseline predicted radiation dose to post darovasertib treatment dose by central simulation (Treatment Arm only)
9. Cohort 1:To demonstrate a reduction in the proportion of subjects with OCT findings consistent with ME by BICR in the Treatment Arm vs the Control Arm
10. Cohort 1:To demonstrate a reduction in the proportion of subjects with OCT findings consistent with ME by BICR in the Treatment Arm vs the Control Arm

Conditions and MedDRA coding

Uveal Melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Be at least 18 years of age
2. 2. 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
3. 3. At high risk of metastasis defined by at least one of the following: • Monosomy 3 • Class 2 GEP • Stage 3 by AJCC (Appendix 1 [Section 15.1]) NOTE: Monosomy 3 as determined by karyotyping, chromogenic or fluorescence in situ hybridization (CISH or FISH), Next-Generation Sequencing (NGS), chromosomal microarray analysis (CMA), or array Comparative Genomic Hybridization (aCGH). Other methodologies may be acceptable after discussion with the IDEAYA Medical Monitor. Class 2 GEP as determined by Castle Decision Dx-UM® when this testing has been performed as part of local standard of care practice. Molecular testing is preferred to determine high risk for metastasis status; however, AJCC stage 3 is considered qualifying if molecular testing is not completed per local standard of care practice.
4. 4. For Cohort 1 (PB): • Have a diagnosis of primary UM and being considered for treatment with PB and with the following tumor characteristics: o In geographic regions where ruthenium PB is standard of care therapy  Tumor thickness ≥ 4 mm and ≤ 6 mm  Tumor basal diameter up to 16 mm o In geographic regions where iodine PB is standard of care therapy  Tumor thickness ≥ 4 mm and ≤ 10 mm  Tumor basal diameter up to 16 mm o Have at least 20/80 vision in the affected eye o Projected radiation dose of ≥ 30 Gy to the macula or optic disc/nerve based on central dosimetry calculations
5. 5. For Cohort 2 (enucleation): • Have a diagnosis of primary UM and being considered for treatment with enucleation and with the following tumor characteristics: o In geographic regions where ruthenium PB is standard of care therapy  Tumor thickness > 6 mm and ≤ 10 mm  Tumor basal diameter up to 16 mm o In geographic regions where iodine PB is standard of care therapy  Tumor thickness > 10 mm and ≤ 15 mm  Tumor basal diameter up to 16 mm
6. 6. Able to safely swallow orally administered medication
7. 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. 8. Have adequate organ function at the time of the Screening assessments.
9. 9. Agree to the following contraception while receiving darovasertib and for the period defined after the final dose: • Women of childbearing potential, defined as women physiologically capable of becoming pregnant, who are sexually active with a non-sterilized male partner, must use, or continue to use if already using, highly effective methods of contraception during study treatment and for 6 months after the final dose of study treatment (Appendix 4 [Section 15.4]). Cessation of birth control after this point should be discussed with the subject’s physician. NOTE: Systemically acting hormonal contraceptives should always be combined with a barrier method (preferably male condom). • Male subjects: Are surgically sterile or must agree to use double-barrier contraception methods from the time of informed consent, throughout the treatment period, and for 3 months following administration of the last dose of study treatment.

Exclusion criteria 22

1. 1. Previous treatment for UM
2. 2. Evidence of metastatic UM
3. 3. Tumor originating from the iris
4. 4. Sub-retinal or vitreous bleeding that prevents monitoring of treatment effect
5. 5. Subfoveal location and abutment to the optic disc (Cohort 1 only)
6. 6. Attributes that necessitate enucleation regardless of response to therapy (e.g., neovascular glaucoma, extraocular involvement, hemorrhage, blind painful eye, tumor involvement of the anterior chamber, or evidence of optic nerve invasion)
7. 7. Inability to visualize all tumor dimensions on imaging studies for tumor measurements
8. 8. Pre-planned (i.e., prophylactic) use of VEGFi and/or corticosteroids for radiation induced ocular toxicities (Cohort 1 only)
9. 9. Previous, current, or anticipated administration of intravitreal VEGFi and/or corticosteroids for diabetic retinopathy or another ocular disorder (Cohort 1 only) NOTE: Use of corticosteroids at the time of PB placement is allowed if considered local standard of care practice.
10. 10. Evidence of progressive secondary underlying ocular disease in either eye that would confound longitudinal VA assessments (e.g., macular degeneration, neovascular age-related macular degeneration, central retinal vein occlusion, pre-existing glaucoma, or neovascular glaucoma)
11. 11. Moderate to severe diabetic retinopathy or proliferative diabetic retinopathy (Appendix 5 [Section 15.5]) • Moderate diabetic retinopathy is defined by at least one hemorrhage or microaneurysm and/or at least one of the following: retinal hemorrhages, hard exudates, cotton wool spots, or venous beading. • Severe diabetic retinopathy is defined by any of the following but no signs of proliferative diabetic retinopathy: > 20 intraretinal hemorrhages in each of the 4 quadrants, definite venous beading in 2 or more quadrants, or prominent intraretinal microvascular abnormality in one or more quadrants. • Proliferative diabetic retinopathy is defined by either neovascularization or vitreous/preretinal hemorrhage.
12. 12. Presence of a malignant disease, other than the one being treated in this study, with the following exceptions: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment, completely resected basal cell and squamous cell skin cancers, any malignancy considered to be indolent and never required systemic therapy, and any type of completely resected carcinoma in situ.
13. 13. Known acquired immunodeficiency syndrome (AIDS)-related illness NOTE: Human immunodeficiency virus (HIV) seropositive subjects who are healthy and have a low risk for AIDS-related outcomes may be considered eligible. Participants with known HIV, CD4 counts ≥200/μL and undetectable viral loads who are stable on antiretroviral regimen may be included after discussion with the IDEAYA Medical Monitor regarding current and past CD4 and T cell counts, history of any AIDS-defining conditions, and status of HIV treatment. The potential for drug-drug interactions (DDIs) will also be taken into consideration.
14. 14. Active infection requiring systemic anti-microbial therapy (Subjects requiring systemic antimicrobial therapy for infection must have completed therapy at least 1 week prior to the first dose of study drug for subjects in the Treatment Arms or PLT for subjects in the Control Arms.)
15. 15. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as diagnosed by institutional protocol.
16. 16. Major surgery within 4 weeks prior to study entry (Minimally invasive procedures, such as bronchoscopy or tumor biopsy are not considered major surgery.)
17. 17. Inability to discontinue medications belonging to any of the following categories prior to and while receiving darovasertib: • Known strong inducers or inhibitors of CYP3A4/5 • Known substrates of CYP3A4/5 with a narrow therapeutic index • Known substrates of P-gp or BCRP with a narrow therapeutic index NOTE: a wash-out period is required
18. 18. Pregnant or breastfeeding prior to and while receiving darovasertib
19. 19. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: • History or presence of ventricular tachyarrhythmia • Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute [bpm]); subjects with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria. • Presence of angina pectoris or acute myocardial infarction ≤ 6 months prior to study treatment • Presence of congestive heart failure requiring treatment; (For New York Heart Association Class 1, inclusion can be considered upon discussion and agreement with the IDEAYA Medical Monitor.) • Presence of other clinically significant heart disease (e.g., uncontrolled arrhythmia or hypertension, history of labile hypertension or poor compliance with an antihypertensive regimen, and/or symptomatic bradycardia) Presence of a drug eluting stent for cardiovascular purposes placed ≤ 2 months prior to study treatment • A corrected QT interval of > 470 msec per Fridericia’s formula (QTcF) on baseline ECG (mean of baseline values) (Appendix 6 [Section 15.6]) NOTE: If electrolytes are abnormal, they may be corrected, and baseline ECGs should be repeated. NOTE: For subjects with a significantly prolonged QRS complex (> 110 msec) due to a bundle branch block or an intraventricular conduction delay, an “adjusted” QTcF for the QRS widening will be used to evaluate study eligibility. “Adjusted QTcF” = measured QTcF – [measured QRS – 90 msec].
20. 20. Asymptomatic persistent heart rate < 55 bpm, unless discussed with and agreed to enroll by the IDEAYA Medical Monitor
21. 21. History of stroke ≤ 6 months before study enrollment
22. 22. Allergy to mammalian meat products or gelatin

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cohort 1: Proportion of moderate to high risk of visual impairment (MHRVI) subjects with loss of Best Corrected Visual Acuity (BCVA) of ≥ 15 letters using Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA (%VL15) measured from the time of randomization and completion of PB
2. Cohort 2: Eye preservation rate

Secondary endpoints 10

1. Both Cohorts: ORR_UM, defined as the rate of best overall response (complete response [CR] or partial response [PR]) Response defined as: o CR: Complete regression of tumor by ultrasound (US) and fundus photography (FP); o PR: Decrease in product of diameters by US and/or FP by ≥ 20% or decrease in thickness by US by ≥ 20% from baseline;
2. Both Cohorts: EFS, defined as the time from randomization to the first documented date of treatment failure (including disease progression, local/distant recurrence, or death, whichever occurs first)
3. Both Cohorts: Incidence of all treatment-emergent AEs (TEAEs), serious adverse events (SAEs) and clinically significant laboratory test abnormalities, and changes to electrocardiograms (ECGs) and vital signs
4. Both Cohorts: • ORR_UM • DCR, defined as the proportion of CR, PR, or SD
5. Both Cohorts: Proportion of subjects with improvement in ETDRS BCVA letters and/or Snellen lines
6. Cohort 1: Proportion of subjects with clinically significant ME (%ME defined optical coherence tomography [OCT] finding, vision loss, and initiation of vascular endothelial growth factor inhibitor [VEGFi] administration) measured from the time of randomization and completion of PB
7. Cohort 1: Proportion of subjects with 20/200 vision or worse (%20/200) from the time of randomization and completion of PB
8. Cohort 1: Proportion of subjects with significant reduction of radiation dose (defined as a ≥ 20% reduction) delivered to key eye structures including, but not limited to, the macula, optic disc/nerve, and lens
9. Cohort 1:Proportion of subjects with ME on OCT from the time of completion of PB ME by OCT defined as the presence of intraretinal fluid (cystoid edema) on OCT
10. Cohort 1:Proportion of subjects with radiationrelated ocular toxicities at 6, 12, 18, 24, 30, and 36 months post PB • The incidence and severity of radiation induced ocular toxicities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ideaya Biosciences Inc.

Sponsor organisation

Ideaya Biosciences Inc.

Address

5000 Shoreline Court Suite 300

City

South San Francisco

Postcode

94080-1956

Country

United States

Scientific contact point

Organisation

Ideaya Biosciences Inc.

Contact name

Candice Montagna

Public contact point

Organisation

Ideaya Biosciences Inc.

Contact name

Candice Montagna

Third parties 7

Locations

10 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications