For The First Time, A Potential Treatment Option For All Uveal Melanoma Patients

In general, melanoma is considered one of the great cancer success stories of our time. Dr. Puzanov points out that today, nearly half of all patients diagnosed are eventually cured. But not every type of melanoma has shared in that progress.

Uveal melanoma, a rare form of the disease that starts in the eye, behaves very differently from the skin melanoma most people are familiar with. It is more aggressive, harder to treat, and for decades, largely resistant to every treatment doctors tried.

The First Breakthrough

Researchers have been working to crack uveal melanoma for a long time, but each attempt failed.

The first real breakthrough came in 2022 with the approval of tebentafusp, an immunotherapy drug. Tebentafusp, though, could only be used for patients who carry a specific genetic marker called HLA-A*02:01. That’s roughly 40% of uveal melanoma patients. For the remaining 60%, there was still nothing.

“That 60% didn’t have anything approved for them until now,” Dr. Puzanov says. “And that’s the darovasertib, crizotinib.”

Darovasertib + Crizotinib: What To Know

The new drug combination — darovasertib plus crizotinib — has now shown promising results specifically for patients who do not carry the HLA-A02:01 marker, offering a potential first approved frontline treatment for this group. Notably, early data also suggest the combination may benefit HLA-A02:01-positive patients, raising the possibility it could eventually help all uveal melanoma patients.

In the phase 2/3 OptimUM-02 clinical trial, patients taking darovasertib plus crizotinib went nearly 7 months without their cancer progressing — 6.9 months compared to 3.1 months for patients on standard therapy. The combination nearly doubled the time patients stayed stable. Tumor shrinkage was seen in 37% of patients on the new drugs, versus just 7% on standard treatment.

“That’s both clinically and statistically significant improvement,” Dr. Puzanov says. “When and if this drug becomes available to general oncologists, I think they’ll be rejoicing.”

Side Effects & Availability

Both drugs come in pill form, which makes them more convenient than intravenous (IV) treatments.

The main side effects are gastrointestinal — nausea, vomiting, and diarrhea — but these are well understood and manageable.

“With the right supportive measures, everybody survives, and that’s important,” Dr. Puzanov says. “The goal is not only to prolong life, but to prolong quality life — a life which has meaning.”

Because uveal melanoma is rare, most general oncologists may not yet be familiar with these developments. Dr. Puzanov’s advice to patients is to seek out a specialized cancer center.

“The best approach with a rare cancer is to find centers that have the necessary expertise,” he says. Roswell Park, for example, can typically see new patients within a week, either in person or virtually.

Questions To Ask Your Doctor

• Am I a candidate for the darovasertib plus crizotinib combination?
• Should I consider joining a clinical trial?
• What are the risks v. benefits of this treatment approach?

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