In July, Exelixis is expected to announce results from the "METEOR" phase III study of Cometriq in second-line kidney cancer. This study is Exelixis' next chance to transform Cometriq into a commercially successful cancer drug following the failure of prostate cancer studies last year. Cometriq is approved as a treatment for medullary thyroid cancer but generated just $25 million in 2014 sales because the targeted patient population is so small.
The METEOR study enrolled 650 patients with kidney cancer who previously received but no longer respond to at least one VEGF-targeted drug, such as Pfizer's Sutent. The enrolled patients are randomized to treatment with either Cometriq or Afinitor, a currently approved kidney cancer drug from Novartis. The study's primary endpoint is progression-free survival (PFS) with overall survival serving as the most important secondary endpoint. The study does not allow Afinitor patients to cross over and receive Cometriq on disease progression -- an important design element which will provide cleaner and more convincing survival data (as long as it's positive.)
Exelixis modeled the study on the assumption that Cometriq could reduce the risk of kidney cancer disease progression or death by 33% compared to Afinitor. At the median, Exelixis assumes Afinitor PFS will be five months and that Cometriq can win with a comparative PFS of 7.5 months.
Will these assumptions hold up? Most of the currently approved kidney cancer drugs, including Afinitor, delay tumor progression by between four and five months in the second-line setting following first-line treatment with Sutent, based on published studies.
In 2012, Exelixis conducted a single-arm, open-label, phase I study of Cometriq (known then as cabozantinib) in 25 kidney cancer patients previously treated with a median of two prior therapies. Eighty-eight percent of the enrolled patients were treated previously with at least one VEGF-targeted drug, mirroring the patients in the METEOR study. In this phase I study, Cometriq demonstrated a median PFS of 12.9 months and median overall survival of 15 months. The study was presented at the 2012 ASCO annual meeting and published in 2014 in the Annals of Oncology.
Exelixis has built a comfortable cushion into the phase III study to ward off the risk phase I results exaggerated Cometriq's true efficacy in kidney cancer. [A higher dose of the drug was given to patient in the phase I study compared to what's being used in the phase III study.] I give Cometriq better than even odds of showing a PFS benefit over Afinitor but will that be enough to 1) satisfy the FDA secure approval; and 2) convince doctors to prescribe Cometriq over multiple other kidney cancer drugs already approved?