NEW YORK – Ideaya Biosciences on Tuesday began an investigator-sponsored trial of darovasertib as a neo-adjuvant and adjuvant treatment for patients with primary, non-metastatic uveal melanoma.
The Phase I trial is being led by the Kinghorn Cancer Centre of St. Vincent's Hospital in Sydney with participating sites at Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne, Australia.
Darovasertib is thought to be effective in uveal melanoma because of the prevalence of GNAQ and GNAQ11 mutations in this tumor type. The drug inhibits activation of protein kinase C (PKC), which is associated with mutations in GNAQ and GNAQ11.
"The concept for this study originated from anecdotal observations in a metastatic uveal melanoma patient treated with darovasertib who also had an intact primary lesion in the eye, where a reduction in the eye lesion was observed at an initial scan with improvement in visual symptoms," Anthony Joshua, the trial's principal investigator and head of the department of medical oncology at Kinghorn Cancer Centre, said in a statement.
Another trial investigator, Mark Shackleton, director of oncology at Alfred Health, added that researchers are seeing early signals of clinical activity in the first patient enrolled in the study. "Our coordinated patient care with eye specialists at the Royal Victorian Eye and Ear Hospital on this trial has enabled a potential paradigm-shifting approach to reduce the size of ocular tumors prior to primary treatment, which we hope will lead to better outcomes for patients," Shackleton said in a statement.
Ideaya, based in South San Francisco, California, is further exploring darovasertib with Pfizer's ALK inhibitor Xalkori (crizotinib) in a Phase II study in metastatic uveal melanoma and is slated to report data this month. The company has a Phase II trial underway exploring the drug's activity broadly in cMET-driven solid tumors, including hepatocellular carcinoma and non-small cell lung cancer. Ideaya is also planning to present proof-of-concept data this month demonstrating darovasertib's efficacy as a monotherapy in the neo-adjuvant or adjuvant uveal melanoma setting.
In April, the US Food and Drug Administration granted darovasertib orphan drug designation as a treatment for metastatic uveal melanoma.