Drug Duo Represents ‘Potential Paradigm Shift’ for Rare Eye Cancer

Uveal melanoma is a rare condition for which more therapies are needed.

The drug combination of darovasertib and Xalkori (crizotinib) improved outcomes for patients with metastatic uveal melanoma, a rare cancer of the eye, according to results from a phase 2 clinical trial.

The findings are particularly promising for a subgroup of patients that currently has no approved treatment regimens.

Interim findings from 20 evaluable patients enrolled in the ongoing trial who received darovasertib and Xalkori in the frontline setting showed that 45% of participants responded to the drug duo, with a disease control rate of 90%. Additionally, the average progression-free survival (time a patient lives before they die or disease worsens) was approximately seven months.

"The observed efficacy in first-line metastatic uveal melanoma patients – including confirmed (response rate) of 45% and median PFS of (about) seven months – is clinically significant and represents a potential paradigm shift for treating (metastatic uveal melanoma) patients,” Dr. Meredith McKean, director, melanoma and skin cancer research at Sarah Cannon Research Institute, said in a press release issued by Ideaya, the manufacturer of darovasertib.

Within a group of 63 patients who received the combination at any point during treatment (either upfront or after other therapy/therapies), 30% responded to treatment, with an 87% disease control rate. The average progression-free survival for this group was seven months as well.

In patients who only had metastases in the liver, the response rate was 35% with a 100% disease control rate. In this group, the average progression-free survival was 11 months.

Ideaya presented these findings to the U.S. Food and Drug Administration (FDA), which, in turn, provided the manufacturer with resources for a potential accelerated approval for darovasertib plus Xalkori in the frontline setting for patients with HLA-A2—negative metastatic uveal melanoma — a group of patients that currently has no FDA-approved therapies.

"These clinical data, considered with the FDA's guidance from our recent Type C meeting, provides Ideya with a registrational trial design in first-line HLA-A2 negative (metastatic uveal melanoma) patients which includes a path to potential accelerated approval based on median (progression-free survival) as the primary endpoint," said Dr. Darrin Beaupre, chief medical officer of Ideaya, in the release.

Ideaya is now planning on starting a phase 2/3 clinical trial evaluating darovasertib plus Xalkori for patients with HLA-A2—negative metastatic uveal melanoma that has not been previously treated. The main goal of the phase 2 portion of this trial is progression-free survival. Then, when patients move on to the phase 3 part, researchers will also analyze overall survival (time from treatment until death of any cause). The pharmaceutical company is hoping that findings from the trial will support an accelerated approval in this indication.

According to the release, approximately 0% to 5% of patients with HLA-A2—negative metastatic uveal melanoma tend to respond to the current available therapies, with an average progression-free survival ranging from two to three months.

READ MORE: A Look at the ‘Collateral Damage’ From Uveal Melanoma Treatment

Darovasertib plus Xalkori tended to have a manageable side effect profile, according to the release. The majority of side effects were mild (grade 1 or 2), with 31% of patients reporting a moderate (grade 3) side effect. No patients experienced a serious (grade 4) side effect, though one person did die from the drug duo.

Six percent of patients stopped treatment with either of the drugs due to side effects.

“The interim data for the darovasertib and (Xalkori) combination treatment in (metastatic uveal melanoma) suggests a compelling clinical efficacy and tolerability profile," McKean said.

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