FDA Grants Orphan Drug Designation to Darovasertib for Uveal Melanoma Treatment


With an FDA orphan drug designation for the treatment of patients with uveal melanoma, darovasertib is being actively investigated in a phase 1/2 clinical trial.

The FDA has granted orphan drug designation to darovasertib (IDE196), for the treatment of patients with uveal melanoma, according to an announcement by IDEAYA Biosciences, Inc.1

Darovasertib is a potential first-in-class protein kinase C inhibitor, which is being investigated in a phase 1/2 clinical trial in combination with a c-Met inhibitor or a MEK inhibitor.

The phase 1/2, multi-center, open-label basket study (NCT03947385) aims to enroll 254 patients with the goal of determining the safety and anti-tumor activity of darovasertib in patients with solid tumors harboring GNAQ or GNA11 mutations or PRKC fusions, which includes patients with metastatic uveal melanoma, cutaneous melanoma, colorectal cancer, and other solid tumors. Across 7 cohorts, patients will receive either darovasertib alone, darovasertib plus binimetinib (Mektovi), or darovasertib plus crizotinib (Xalkori).2

During both the dose-escalation and dose-expansion phases of the study, darovasertib will be administered orally, twice daily (BID) for each 28-day cycle. The co primary end points determining the dose-limiting toxicity, maximum-tolerated doses, recommended phase 2 dose, the plasma concentration of darovasertib monotherapy, overall response rate (ORR) by blinded independent review committee, and duration of response (DOR). The secondary end points included ORR, DOR, as well as ORR, DOR, and disease control rate by investigator assessment. The secondary safety end point are safety and tolerability determined by the number of patients with adverse events. The study is also exploring treatment-related pharmacodynamic effects in all patients as a secondary end point.

Other outcomes being investigated in the study of darovasertib include progression-free survival, overall survival, reduction in tumor burden by total volumetric measurement, treatment-related gene signatures and/or molecular profiling, and treatment-related changes in tumor tissue or cell-free DNA from blood.

To be eligible for inclusion in the study, patients are required to be at least 18 years of age or older with measurable disease, an ECOG performance status of at least 3 months, and adequate organ function and contraceptive measures for non-sterilized male and female patients of childbearing potential at the time of screening. To be eligible to receive the binimetinib combination, patients must also have adequate cardiac function represented by a left ventricular ejection fraction ≥ 50%. For the crizotinib combination arms, patients must have received prior chemotherapy, or other therapies and major surgeries 4 weeks prior to the start of crizotinib in the study, and any preexisting peripheral neuropathy must grade 1 or lower for patients to be eligible for inclusion.

The study is being conducted at 12 sites in the United States, Canada, and Australia. The 11 sites actively recruiting patients are located in Arizona, California, Florida, Missouri, New York, Ohio, Pennsylvania, Tennessee, Texas, New South Wales, and Ontario.

"We are excited to advance darovasertib towards a potential registration-enabling trial in metastatic uveal melanoma, and the orphan-drug designation is an important step towards our goal to bring this novel therapy to patients," said Matthew Maurer, MD, vice president and head of Clinical Oncology and Medical Affairs, at IDEAYA Biosciences, in a press release.1


1. IDEAYA Biosciences receives orphan drug designation for darovasertib, a PKC inhibitor, for the treatment of uveal melanoma. News release. IDEAYA Biosciences. May 02, 2022. Accessed May 2, 2022. https://bit.ly/3kzf33A

2. Study of IDE196 in patients with solid tumors harboring GNAQ/11 mutations or PRKC fusions. Clinicaltrials.gov. Updated December 29, 2021. Accessed May 2, 2022

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