Darovasertib for Ocular Melanoma

Recruiting at 37 trial locations

Overseen By Jasgit Sachdev, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: IDEAYA Biosciences

Must not be taking: PKC inhibitors

Disqualifiers: Concurrent malignancy, HIV, Hep B/C, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called darovasertib for individuals with primary uveal melanoma, a type of eye cancer. The goal is to determine if taking darovasertib before or after surgery can better manage the cancer. It targets those needing eye surgery or radiation for their melanoma and who can take oral medication. Participants should not have other major eye diseases or certain health conditions, such as heart problems. This trial offers an opportunity for those who haven't undergone similar treatments and are interested in exploring new options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are prohibited by the study. If you cannot discontinue these medications, you may not be eligible to participate.

Is there any evidence suggesting that darovasertib is likely to be safe for humans?

Research has shown that darovasertib is generally well-tolerated by people with uveal melanoma, a type of eye cancer. In one study, 83% of patients experienced tumor shrinkage, which is promising. Notably, 54% of these patients saw a tumor reduction of 20% or more. These results suggest that the treatment is both effective and manageable for patients.

Darovasertib has been tested at different doses. Earlier research found that taking 300 mg once a day or 200 mg twice a day is effective and safe. No specific safety concerns have been identified, which is encouraging for those considering this treatment. However, as with any clinical trial, researchers will continue to monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Darovasertib is unique because it targets a specific protein called PKC (protein kinase C), which plays a critical role in the growth of ocular melanoma cells. Unlike traditional treatments like surgery, radiation, or chemotherapy, darovasertib is an oral medication, potentially offering a more convenient option for patients. Researchers are excited about darovasertib because it represents a novel approach to treating ocular melanoma, with the potential to specifically disrupt cancer cell growth and spread, possibly leading to more effective outcomes with fewer side effects.

What evidence suggests that darovasertib might be an effective treatment for ocular melanoma?

Research has shown that darovasertib, which participants in this trial will receive, may help treat uveal melanoma, a type of eye cancer. Studies have found that 83% of patients experienced tumor shrinkage, with more than half seeing at least a 20% reduction in size. Additionally, darovasertib preserved the eyes of 57% of patients. It blocks PKC, a protein that aids tumor growth. This treatment has also been associated with longer survival times compared to past data. These findings suggest that darovasertib could be a promising option for people facing this challenging condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Jasgit Sachdev, MD

Principal Investigator

IDEAYA Biosciences

Are You a Good Fit for This Trial?

This trial is for individuals with primary localized uveal melanoma who need enucleation or plaque brachytherapy. Participants should be in good physical condition (ECOG 0-1), not have other serious eye diseases, and must not be pregnant or nursing. They should agree to use birth control, be able to take oral medication, and have proper organ function. Those with concurrent cancer, significant heart issues, malabsorption disorders, active HIV/Hep B/C infections or previous PKC inhibitor treatments are excluded.

Inclusion Criteria

I can take medicine by mouth.

I am fully active or can carry out light work.

My organs are working well.

Exclusion Criteria

I do not have any other types of cancer.

You have any other health issues that might make it hard to understand or get accurate results from the study.

I have a condition that affects how my body absorbs nutrients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive IDE196 (darovasertib) in a neoadjuvant setting to assess tumor response and potentially convert enucleation to radiation

6 months

Primary Local Therapy

Participants undergo primary local therapy, either enucleation or plaque brachytherapy, based on tumor response

Not specified

Adjuvant Treatment

Participants receive an additional 6 months of IDE196 (darovasertib) treatment following primary local therapy

6 months

Follow-up

Participants are monitored for visual outcome, disease recurrence, and development of metastatic disease

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Darovasertib

Trial Overview The trial is testing Darovasertib (IDE196) as a new treatment option for patients with localized ocular melanoma. It's given before (neoadjuvant) and after (adjuvant) standard procedures like enucleation or plaque brachytherapy to see if it can improve outcomes.

How Is the Trial Designed?

Group I: darovasertib Experimental Treatment 1 Intervention

IDE196 (darovasertib) oral open label

Who Is Running the Clinical Trial?

IDEAYA Biosciences

Lead Sponsor

Trials

6

Recruited

1,300+

Published Research Related to This Trial

An 81-year-old woman treated with dabrafenib and trametinib for metastatic melanoma experienced a retinal branch vein occlusion and macular edema in one eye, highlighting a potential ocular complication of these medications.

After discontinuing the treatment, her macular edema was effectively managed with anti-VEGF injections, demonstrating that timely intervention can lead to a good response in patients experiencing such side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal Vein Occlusion in a Patient on Dabrafenib and Trametinib Therapy for Metastatic Melanoma. Molero-Senosiain, M., Salazar, ML., Camacho, I., et al.[2022]

In a review of clinical trials involving 855 patients with advanced melanoma, 22% of those treated with vemurafenib experienced ocular adverse effects, with uveitis being the most common at 4%.

Despite these ocular side effects, they were manageable, allowing patients to continue their vemurafenib treatment without interruption, indicating a level of safety in the management of these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. Choe, CH., McArthur, GA., Caro, I., et al.[2022]

Uveal melanoma is the most common primary eye tumor in adults, with a high risk of metastasis, particularly to the liver, leading to a median survival of only 4-5 months for affected patients.

Current treatments for metastatic uveal melanoma are limited, but new targeted therapies and immunotherapies, such as ipilimumab, show promise in improving outcomes, with ongoing research into their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uveal melanoma. Spagnolo, F., Caltabiano, G., Queirolo, P.[2017]

Darovasertib, a new oral inhibitor of protein kinase C (PKC), has received orphan drug designation for treating uveal melanoma, a cancer with a high risk of metastasis and poor prognosis.

In clinical trials, darovasertib has shown greater potency and a better safety profile compared to other PKC inhibitors, and when combined with MEK inhibitors, it produces a synergistic effect, enhancing its potential efficacy in treating uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darovasertib, a novel treatment for metastatic uveal melanoma. Cao, L., Chen, S., Sun, R., et al.[2023]

A case report demonstrated that the combination of neoadjuvant darovasertib and crizotinib effectively reduced the size of a large uveal melanoma in a patient, allowing for vision-saving treatment instead of enucleation.

After 6 months of treatment, the tumor shrank significantly, enabling the use of plaque brachytherapy, which suggests that this combination therapy could improve visual outcomes for patients with primary uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma. Hiong, A., O'Day, R., Fog, LS., et al.[2023]

The phase II trial of the MEK inhibitor selumetinib shows promising results for patients with metastatic uveal melanoma, a rare and aggressive form of eye cancer.

This trial indicates that selumetinib may provide a new treatment option for patients facing this challenging diagnosis, highlighting its potential efficacy in combating this fatal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uveal melanoma therapy on the horizon? [2018]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

Citations

1. ir.ideayabio.com ir.ideayabio.com/2025-10-20-IDEAYA-Biosciences-Reports-Positive-Median-Overall-Survival-Data-from-Phase-2-Trial-of-the-Darovasertib-and-Crizotinib-Combination-in-First-line-Metastatic-Uveal-Melanoma-at-the-2025-Society-for-Melanoma-Research-Congress

News Releases Combination demonstrated median overall survival (OS) of 21.1 months, compared to reported historical mOS of approximately 12 months in ...

2. prnewswire.com prnewswire.com/news-releases/ideaya-biosciences-announces-positive-phase-2-data-for-darovasertib-in-the-neoadjuvant-setting-of-primary-uveal-melanoma-in-a-proffered-paper-oral-presentation-at-esmo-2025-302588310.html

IDEAYA Biosciences Announces Positive Phase 2 Data ... 83% (78/94) of patients demonstrated ocular tumor shrinkage, with 54% (51/94) achieving ≥20% tumor shrinkage; 57% (24/42) eye preservation ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9510

A phase 2 safety and efficacy study of neoadjuvant ... The results suggest that PKC inhibition with darovasertib can induce clinically meaningful tumor shrinkage in patients with primary UM patients who otherwise ...

4. onclive.com onclive.com/view/neoadjuvant-darovasertib-produces-preliminary-responses-in-uveal-melanoma

Neoadjuvant Darovasertib Produces Preliminary ... Darovasertib demonstrated significant ocular tumor shrinkage and reduced radiation dose in uveal melanoma patients, improving visual outcomes.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10147608/

LXS196 for Metastatic Uveal Melanoma - finally some ... Metastatic uveal melanoma continues to have a poor prognosis with distinct pathophysiology from cutaneous melanoma and limited effective treatment options.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05907954

NCT05907954 | (Neo)Adjuvant IDE196 (Darovasertib) in ... All patients will have long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease. Official Title.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419210/

Darovasertib, a novel treatment for metastatic uveal ... Doses of 300 mg once a day or 200 mg twice a day are assumed to be efficacious, based on the preclinical results, while the actual efficacious ...