ODAC Advises FDA to Wait for Results of TIGER-3 for Rociletinib in NSCLC

The committee voted 12-1 in favor of delaying approval of the drug and waiting on results from the phase 3 study.

Clovis Oncology announced in a press release that the FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted 12-1 for the FDA to wait on results from the ongoing phase 3 study of rociletinib, before making an early approval decision on the drug for non-small cell lung cancer (NSCLC).

There were indications last week that members on the ODAC might have concerns with the drug’s performance. A briefing document posted to the FDA’s website raises concerns with whether the outcomes presented in the documents submitted to the FDA were sufficient to prove clinical benefit and superiority over the existing treatments available for NSCLC patients who harbor a T790M—mutated form of the epidermal growth factor receptor (EGFR). Additionally, the committee had concerns with QTc prolongation and ventricular arrhythmias in patients exposed to the drug’s metabolites.

“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.”

“We are disappointed with today’s outcome, as we believe in the strength of the data we presented for rociletinib,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We will work with the FDA to evaluate the best path forward as it continues to review our application.”

This is a setback for the company because patient enrollment for the phase 3 TIGER-3 trial is expected to continue into 2018.

Panel member Michele Orza, ScD, of the Patient-Centered Outcomes Research Institute was the only one who voted for the drug’s approval based on existing data. “I think 2018-2019 is a long time to wait, which is not to say that I would vote for accelerated approval today. There are a lot of questions that we have to work out. I’m not confident that the [phase 3] study, even when it's done, will give us a lot of the answers we're looking for,” he said. “I’m concerned that there is a population that could be benefiting from this, and we need to do some more work to identify that group and consider accelerated approval for them.”

Rociletinib is an oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014. Early data from the phase 1 studies of rociletinib created a lot of splash at the American Society of Clinical Oncology’s annual meeting in 2014.

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