Are FDA Reviewers Concerned About the Value of Clovis Oncology's EGFR Inhibitor Rociletinib?

April 8, 2016

A preliminary briefing document expresses concerns over clinical benefit over existing treatments, safety, and overall risk-benefit of the drug for the subset of lung cancer patients for whom the drug has been developed.

Ahead of the Oncologic Drugs Advisory Committee or ODAC meeting on April 12, 2016, the FDA has posted briefing materials on its website with respect to the accelerated approval of Clovis Oncology’s epidermal growth factor receptor (EGFR) inhibitor rociletinib, for treatment of patients with non-small cell lung cancer (NSCLC) who harbor a T790M mutation in EGFR, and whose disease has progressed after treatment.

The briefing document proposes a discussion on the activity of the drug based on the overall response rate and duration of response, and whether these outcomes are sufficient to predict clinical benefit and superiority over available therapy. The comparator arms in the submitted studies include single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) in patients with T790M mutation—positive NSCLC. The other considerations of the discussion include ensuring effectiveness of the proposed dose, safety of the drug, and whether the dose modification strategy to mitigate drug toxicity is well characterized.

A point of contention is the QTc prolongation and ventricular arryhtmias in patients exposed to the drug’s metabolites. The reviewers would like the advisory committee to discuss these issues during the meeting, along with the overall benefit-risk profile of rociletinib in the proposed patient population.

Clovis’ drug is not the first in its class—AstraZeneca’s osimertinib (Tagrisso) was approved late last year to treat the same population of T790M—mutated NSCLC patients who have progressed on other treatment.