Uveal melanoma is a rare cancer that starts in the eye. Although it behaves very differently from skin melanoma, it can be just as serious—especially when it spreads to the liver or other parts of the body. For many years, treatment options were extremely limited. Darovasertib, a new oral medicine still in clinical trials, is giving doctors and patients a reason to hope for better outcomes.
This guide explains what darovasertib is, how it works, current research results, and what patients may expect.
Read About Ocular Melanoma on OncoDaily
Why Do Patients Need New Treatments?
Unlike skin melanoma, uveal melanoma usually does not respond well to immunotherapy or chemotherapy. Most tumors have specific mutations in genes called GNAQ or GNA11, which act like a stuck accelerator pedal, driving uncontrolled cell growth. Until recently, there were no medications targeting this core problem.
Darovasertib is one of the first drugs designed to block the signals coming from these GNAQ/GNA11 mutations.
What Is Darovasertib?
Darovasertib (IDE196) is an oral targeted therapy. It blocks a protein in cancer cells called protein kinase C (PKC). PKC is part of the main pathway that becomes overactive because of GNAQ/GNA11 mutations. By shutting off this switch, darovasertib aims to:
- Slow cancer growth
- Shrink tumors
- Help patients live longer
- Keep disease under control with manageable side effects
It is not yet approved by the FDA or EMA, but it is being studied in several international clinical trials.
How Does Darovasertib Work?
Think of the GNAQ/GNA11 mutation as a broken signal that constantly tells cancer cells to grow. PKC is the protein that carries that signal forward. Darovasertib blocks PKC, interrupting the message and slowing down the cancer.
This makes it fundamentally different from:
- Immunotherapy, which uses the immune system to attack cancer
- Chemotherapy, which directly kills dividing cells
- Liver-directed therapies, which treat tumors inside the liver
Darovasertib is a personalized medicine because it targets the exact mutations found in most uveal melanoma tumors.
How Is Darovasertib Given?
Darovasertib is taken by mouth, usually twice a day.
Because it is a targeted therapy, patients are monitored regularly through:
- Blood tests
- Liver function tests
- Scans to check tumor response
- Side-effect evaluation
Most patients stay on treatment as long as it is helping and side effects are manageable.
What Do Clinical Trials Show So Far?
Darovasertib Alone
In early studies of patients with metastatic uveal melanoma:
- About 45% of patients had some tumor shrinkage
- Around 12% had significant tumor reduction (partial response)
- Many patients experienced longer periods without growth compared to older treatments (Hidalgo et al., 2022)
These results were better than historical outcomes but still modest—so researchers began studying combinations.
Darovasertib + Crizotinib: The Most Promising Results to Date
Crizotinib is another oral medicine that blocks a protein called cMET, which is often active in melanoma tumors, especially those that spread to the liver. When darovasertib and crizotinib are combined, they appear to work much better together than alone.
What patients experienced in trials:
- Up to 45% of patients had their tumors shrink
- In some newly diagnosed patients, shrinkage reached around 60%
- About 90% achieved disease control, meaning the cancer either shrank or stopped growing
- Responses often lasted many months, with some over a year
For a cancer that historically had a response rate under 5% with older medications, these results are a major step forward.
How Does Darovasertib Compare to Other Treatments?
Here is what patients need to know:
- Immunotherapy works for many cancers, but for uveal melanoma, it helps a small number of patients.
- Tebentafusp, an immunotherapy approved for a specific genetic type (HLA-A*02:01), improves survival but shrinks tumors in only about 9% of patients.
- Liver-directed therapies can temporarily control liver tumors but do not treat the rest of the body.
Darovasertib, especially when combined with crizotinib, may offer higher tumor shrinkage rates and may become a future standard option once trials are complete.
Side Effects: What Patients Report
Most side effects are mild to moderate and manageable with dose adjustments.
Common symptoms include:
- Nausea
- Diarrhea
- Swelling (edema)
- Fatigue
- Changes in liver tests
- Skin rash
Serious side effects are less common and typically reversible. Doctors may adjust the dose, pause treatment, or treat symptoms with supportive medications.
Who Might Benefit From Darovasertib?
Based on genetic features of the cancer, most patients with uveal melanoma are potential candidates, because:
- Over 90% have GNAQ or GNA11 mutations
- The drug does not require a specific HLA type
- It targets the main cancer-driving pathway
However, darovasertib is only available through clinical trials at this time.
Are There Ongoing Trials?
Yes. Several Phase II and Phase III (late-stage) trials are underway, including:
- Darovasertib + crizotinib in newly diagnosed metastatic uveal melanoma
- Darovasertib combinations with immunotherapy
- Studies exploring whether earlier use can prevent metastasis
If final data remain strong, darovasertib could move toward regulatory approval in the next few years.
Read About Immunotherapy for Melanoma on OncoDaily
Takeaway for Patients
Darovasertib is a promising new targeted therapy being studied for metastatic uveal melanoma. It works by blocking a protein (PKC) that is overactive in most tumors. Early results—especially when combined with crizotinib—show significantly higher tumor shrinkage rates than previous treatments. While it is not yet approved, clinical trials are ongoing, and the future outlook appears hopeful.
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Written by Armen Gevorgyan, MD