The Oncologic Drugs Advisory Committee has voted in favor of the FDA waiting for results of an ongoing clinical trial before approving the EGFR inhibitor rociletinib for non-small cell lung cancer.
The Oncologic Drugs Advisory Committee (ODAC) voted 12-1 in favor of the delay, although several committee members acknowledged that the drug demonstrated activity in two phase II trials submitted in support of the application for accelerated approval. Others, however, expressed a desire to see more compelling efficacy data from the larger, phase III trial, and some expressed uncertainty about about how to interpret the drug’s safety, specifically a 33% incidence of QT-prolongation in the single-arm phase II trials.
Additionally, FDA staff review of the trial data “revealed high variability of systemic exposure to rociletinib and its major metabolites. Rociletinib demonstrated nonlinear pharmacokinetics, as systemic exposures did not increase when the dose increased from 500 mg to 1000 mg.”
“I think we have well documented issues about toxicity, dosing, and metabolism that have not been completely addressed,” said ODAC chair Deborah Armstrong, MD, of Johns Hopkins in Baltimore. “Primarily, I don’t think the requirement for accelerated approval to have superiority over current treatment has been shown by the data that we have at this time.”
The ongoing, randomized TIGER-3 trial is scheduled to be completed by late 2018 or early 2019, according to representatives of the drug sponsor, Clovis Oncology.