IDEAYA Bioscience’s rare cancer drug shows benefit in interim Phase II data, with the company announcing the drugs Phase III trial design.

Darovasertib, a protein kinase inhibitor C (PKC) being evaluated in neoadjuvant uveal melanoma (UM), has achieved a tumour shrinkage of at least 30% in around half of patients, and a 61% eye preservation rate following enucleation in interim data from a Phase II trial (NCT05907954).

In step with the trial’s interim results, US-based IDEAYA Biosciences has also concluded a successful Type C meeting with the US Food and Drug Administration (FDA), setting out the design for a pivotal trial of the drug.

Incorporating guidance from the FDA meeting, IDEAYA said it projects the enrolment of approximately 400 patients in the randomised Phase III trial, with darovasertib in the treatment or control arm. The trial will enrol both patients eligible for enucleation and patients eligible for plaque brachytherapy.

IDEAYA said that for the enucleation cohort, the randomisation will be with or without darovasertib as neoadjuvant therapy; and for the plaque brachytherapy cohort, the randomisation will be darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone.

"The successful FDA Type C meeting provides darovasertib with potential registrational path in neoadjuvant UM, using primary clinical endpoints of eye preservation and time to vision loss, with no detriment to EFS in the treatment arms as a secondary endpoint,” said IDEAYA Biosciences chief medical officer Dr Darrin Beaupre.

“Based on the highly promising preliminary clinical efficacy and manageable safety profile observed with darovasertib and the high unmet medical need of neoadjuvant UM, we are excited to advance darovasertib rapidly to a registrational trial in this indication,” Beaupre continued.

The company added that discussions with the FDA were ongoing over the inclusion of overall response rate (ORR) as a potential surrogate and composite endpoint. In addition, the meeting included discussion around the potential for consideration of broad indication label in neoadjuvant UM for subjects with low, intermediate, and high risk for metastatic disease.

IDEAYA is also evaluating darovasertib in four ongoing clinical trials, one of which - darovasertib in combination with Pfizer’s Xalkori (crizotinib) (NCT05987332) in metastatic UM - received fast-track designation from the FDA in 2022.

A rare form of cancer wherein malignant cells form in the uveal tract of the eye, UM accounts for around five per cent of all melanoma cases. Approximately 5,000 cases of UM are diagnosed in the US each year.