Decision on Rociletinib for NSCLC Delayed by FDA

The review period for rociletinib for EGFR T790M-positive non-small cell lung cancer (NSCLC) has been extended by the FDA by 3 months. The extension allows ample time to review additional data submitted by the drug's developer, Clovis Oncology.

Patrick J. Mahaffy

The review period for rociletinib (CO-1686) for EGFR T790M-positive non—small cell lung cancer (NSCLC) has been extended by the FDA by 3 months. The extension allows ample time to review additional data submitted by the drug's developer, Clovis Oncology.

The FDA requested additional data as a result of response rate changes in two ongoing single-arm trials that were the basis for the new drug application. The extension in the review period was expected following this "major amendment," according to Clovis. The FDA had initially granted rociletinib a priority review and an action date of March 30, 2016.

The action date for the new drug application is now June 28, 2016.

In the updated results, evaluable patients treated with the 500 mg dose of rociletinib (n = 79) experienced a confirmed objective response rate (ORR) of 28%. Additionally, in 170 patients treated with the 625 mg dose, the confirmed ORR was 34%. The duration of response for both doses was 9 months.

“As the efficacy data have matured, the number of patients with an unconfirmed response who converted to a confirmed response was lower than expected,” Patrick J. Mahaffy, president and CEO of Clovis, said in a statement when the updated data were released. “We remain confident in rociletinib and its potential to treat patients with mutant EGFR T790M-positive lung cancer.”

In the first study, labeled TIGER-X, 456 patients with EGFR-positive NSCLC received rociletinib across 4 doses (range, 500-1000 mg). The median age of patients was 63 years, 10% had a prior history of diabetes, and 41% had central nervous system (CNS) metastases. The median number of prior therapies was 2 and nearly half of patients had received more than one TKI (44%).

In the earlier data presented at the 2015 ASCO Annual Meeting, patients with T790M mutations (n = 243) experienced an ORR across all dose levels of 53% and a disease control rate of 85%. Specifically for those who received the 500 mg dose (n = 48), the ORR was 60% and a disease control rate was 90%.

At a data cutoff of April 27, 2015, the median progression-free survival (PFS) in evaluable patients with T790M mutations across the 500- and 625-mg doses (n = 270) was 8.0 months. In those without baseline CNS metastases, the median PFS was 10.3 months.

In the safety analysis, the most frequently occurring all-grade adverse events (AEs) in the 500-mg arm were hyperglycemia (35%), diarrhea (33%), fatigue (29%), decreased appetite (15%), muscle spasms (14%), weight loss (10%), and vomiting (8%).

Grade 3 QTc prolongation was seen in 2.5% of patients. No cases of interstitial lung disease were seen at the 500-mg dose level. AEs leading to treatment discontinuation were seen in 2.5% of patients with the 500 mg dose.

Grade 3/4 hyperglycemia occurred in 17% of patients treated with the 500-mg dose. To adjust for this, a monitoring and treatment algorithm was put in place to detect glucose levels and initiate treatment with oral insulin sensitizing agents, when needed. Prior to initiating these measures in September 2014, the rate of grade 3/4 hyperglycemia was 22%. With proper monitoring and treatment, this rate dropped to 8%.

In addition to TIGER-X, data for rociletinib were submitted from the single-arm phase II TIGER-2 trial, according to Clovis. In this ongoing study, rociletinib is being explored as a second-line therapy in patients with EGFR T790M-mutated NSCLC. Data from this study have not yet been announced, with the first patient enrolled in June 2014.

Data from the TIGER-X and TIGER-2 trials were also submitted to the European Medicines Agency for patients with pretreated EGFR T790M-mutant NSCLC. This application was granted an accelerated assessment by the Committee for Medicinal Products for Human Use.


  1. Sequist LV, Goldman JW, Wakelee HA, et al. Efficacy of rociletinib (CO-1686) in plasma-genotyped T790M-positive non-small cell lung cancer (NSCLC) patients (pts). J Clin Oncol. 2015;33 (suppl; abstr 8001).