FDA Delays Decision on New Lung Cancer Drug

FDA requests a more thorough review of rociletinib from ongoing trial.

An FDA decision on a new therapy for lung cancer has been delayed in lieu of further research data.

The FDA requested additional clinical trial data that bolsters the new drug application (NDA) for rociletinib (CO-1686) for pretreated patients with EGFR T790M mutation-positive non—small cell lung cancer (NSCLC).

Rociletinib was previously granted priority review by the FDA with an action date in March 2016. The drug’s developer, Clovis Oncology, was expected to submit the requested data for the 500-mg and 625-mg doses of rociletinib on November 16, 2015, which could delay a regulatory decision by 90 days.

“We remain confident in rociletinib and its potential to treat patients with mutant EGFR T790M-positive lung cancer," said Patrick J. Mahaffy, president and CEO of Clovis Oncology. “We will continue to work diligently with the FDA on our NDA submission.”

The NDA for rociletinib followed promising data from the ongoing phase I/II TIGER-X trial, which showed patients with T790M-mutant NSCLC administered rociletinib at the 500 mg dose (n = 48) showed an objective response rate (ORR) of 60% and a disease control rate (DCR) of 90%.

The FDA asked for a more thorough review due to immature results of unconfirmed and confirmed response rates in the ongoing trial.

Updated data from Clovis found patients treated with the 500 mg dose of rociletinib (n = 79), showed a confirmed response rate of 28%, while 170 patients treated with the 625 mg dose had a confirmed response rate of 34%. Among patients treated with both doses, the duration of response was 9 months.

Most of the recorded responses were unable to be confirmed during follow-up scans as a result of disease progression, as tumor shrinkage did not continue at a rate of >30%.

“As the efficacy data have matured, the number of patients with an unconfirmed response who converted to a confirmed response was lower than expected,” Mahaffy said.

The trial enrolled 456 patients at a median age of 63 years with EGFR-positive NSCLC, who were administered rociletinib across 4 doses (range, 500-1000 mg). Of these patients, 10% had a prior history of diabetes and 41% had CNS metastases.

Additionally, the median number of previous therapies was 2. Approximately half of the patients previously received more than 1 TKI (44%).

Patients with T790M mutations (n = 243) showed an ORR of 53% across all dose ranges, with a DCR of 85%.

At the data cutoff date of April 27, 2015, median progression-free survival (PFS) in patients with T790M mutations across the 500- and 625-mg dose levels (n = 270) was 8 months, while median PFS was 10.3 months in patients with baseline CNS metastases.

An updated safety analysis found the most common all-grade adverse events in the 500-mg arm to be hyperglycemia (35%), diarrhea (33%), fatigue (29%), decreased appetite (15%), muscle spasms (14%), weight loss (10%), and vomiting (8%).

Treatment discontinuation related to adverse events were found in 2.5% of patients administered the 500 mg dose.

Another single-arm phase 2 trial evaluating rociletinib as a second-line treatment for EGFR T790M-mutated NSCLC is still ongoing.