Darovasertib for Ocular Melanoma

Recruiting at 37 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: IDEAYA Biosciences

Must not be taking: PKC inhibitors

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

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests IDE196 (darovasertib) in patients with primary uveal melanoma needing surgery or radiation. The medication is given to help shrink the tumor and prevent it from coming back.

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.

What data supports the effectiveness of the drug Darovasertib for ocular melanoma?

Darovasertib has shown promise in treating uveal melanoma, a type of eye cancer, by effectively inhibiting proteins that help the cancer grow. It has been granted special status by the FDA for this use, and early trials suggest it works well when combined with other treatments. ^{1 2 3 4 5}

Is Darovasertib safe for use in humans?

Darovasertib has been shown to have a better tolerability and safety profile compared to other similar treatments for uveal melanoma, according to current Phase I/II clinical trials. ^{1 2 5 6 7}

Research Team

Jasgit Sachdev, MD

Principal Investigator

IDEAYA Biosciences

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Darovasertib (Protein Kinase Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Darovasertib, a novel treatment for metastatic uveal melanoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Uveal melanoma therapy on the horizon? [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Uveal melanoma. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. [2022]

6. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Retinal Vein Occlusion in a Patient on Dabrafenib and Trametinib Therapy for Metastatic Melanoma. [2022]