The FDA has scheduled an Oncologic Drugs Advisory Committee (ODAC) advisory hearing for April 12 to review the new drug application for rociletinib, a treatment for metastatic EGFR T790-mutated non-small cell lung cancer.
Rolling submission was completed for rociletinib in July 2015. The drug was subsequently granted a priority review by the FDA, though at a preplanned 90-day review meeting, changes in response rates from two pivotal ongoing single-arm trials prompted the FDA to request additional data. This set off the chain of events leading to the scheduling of the ODAC hearing.
In the updated results released by Clovis following the review, evaluable patients treated with 500 mg dose of rociletinib (n = 79) experienced a confirmed objective response rate (ORR) of 28%. In 170 patients treated with the 625 mg dose, the confirmed ORR was 34%. The duration of response for both doses was 9 months.
In the earlier data presented at the 2015 ASCO Annual Meeting and submitted to the FDA, 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%.
“We are actively preparing for this advisory committee meeting and look forward to the discussion about rociletinib,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in a statement. “New treatments are needed for this hard-to-treat patient population, and we believe that rociletinib represents an important new option for patients with mutant EGFR T790M-positive lung cancer.”
Prior to scheduling the ODAC hearing, Clovis had announced that the FDA extended the review period for rociletinib by 3 months, to allow ample time to review the new data. The current action date for rociletinib is June 28, 2016.
In the first study that was submitted to the FDA, 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%).
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. The company did not release new data for PFS.
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.