Rociletinib regulatory update

FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12-1 that FDA should await the outcome of the confirmatory Phase III TIGER-3 trial of rociletinib from Clovis before the agency decides whether to approve the lung cancer therapy. Clovis is seeking accelerated approval of rociletinib to treat EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients who have already received an EGFR-targeting therapy. Its PDUFA date is June 28. Clovis expects to complete enrollment of TIGER-3 in late 2018 and could report data in late 2018 or 1H19. The study’s primary endpoint is progression-free survival (PFS).

Panelists said there were too many lingering uncertainties from the 2 single-arm Phase II studies in rociletinib’s NDA. They were concerned about finding the appropriate dose of the candidate and identifying which patients were at greatest risk for toxicities, namely hyperglycemia and QTc prolongation. Clovis initially sought approval of a 500 mg dose of rociletinib but amended its NDA earlier this year to seek approval of a 625 mg dose, which led to a greater overall response rate (ORR). But panel members and FDA agreed that the difference in the doses’ efficacy was not statistically significant and noted an increase in adverse events for the higher dose. The ORR for the 625 mg dose was 32.4% vs. 22.8% for the 500 mg dose. ...