Ideaya Biosciences has reported positive interim data from the Phase II clinical trial of a darovasertib (IDE196) and crizotinib synthetic lethal combination for patients with metastatic uveal melanoma (MUM).
The latest data is based on 37 subjects who received an expansion dose of 300mg darovasertib and 200mg crizotinib, each given twice daily.
Of these participants, 35 were evaluable.
In the trial, favourable clinical activity was reported in MUM patients in the expansion dose cohort.
According to investigator-analysed data by RECIST 1.1, 89% and 83% of the subjects had tumour shrinkage and disease control rate (DCR), respectively, in any-line MUM.
The overall response rates (ORR) in first-line MUM and any-line MUM were found to be 50% and 31%, respectively.
These findings offer strong clinical proof-of-concept for the combination therapy’s efficacy, the company noted.
Median progression free survival (PFS) was not attained yet and was found to be greater than five months in evaluable first-line MUM patients.
In MUM patients, the darovasertib and crizotinib combination showed a manageable adverse event profile, with a reduced drug-related serious adverse events rate.
Subject enrolment is currently underway in the combination therapy expansion dose cohort of the trial.
The company plans to begin a registration-enabling trial in the first quarter of next year.
A small molecule inhibitor of protein kinase C (PKC), darovasertib is being analysed clinically for MUM and other GNAQ/11 tumours.
The trials are being carried out under a clinical trial partnership and drug supply agreement between Ideaya and Pfizer.
Crizotinib is a small molecule inhibitor of cMET.
Ideaya Biosciences Clinical Oncology and Medical Affairs vice-president, head Dr Matt Maurer said: “The clinical efficacy observed in first-line patients in these interim Phase II data presents an opportunity to pursue a front-line strategy and provides a rationale for a potential registration-enabling clinical trial in MUM.”