The Food and Drug Administration (FDA) has granted Priority Review to the supplemental New Drug Application (sNDA) for cabozantinib (Cabometyx®) for the treatment of differentiated thyroid cancer in patients 12 years and older who have progressed following prior therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate).
The sNDA is supported by data from the phase 3 COSMIC-311 study (ClinicalTrials.gov Identifier: NCT03690388), which compared the efficacy and safety of cabozantinib, a kinase inhibitor, to placebo in patients with radioiodine-refractory differentiated thyroid cancer who had progressed after up to 2 prior vascular endothelial growth factor receptor-targeted therapies. Patients were randomly assigned 2:1 to receive either cabozantinib 60mg orally once daily (n=125) or placebo (n=62).
Results showed that treatment with cabozantinib demonstrated a significant improvement in progression-free survival (PFS; primary endpoint). At a median follow-up of 6.2 months, median PFS was not reached (96% CI, 5.7 months-not estimable) in the cabozantinib arm and was 1.9 months (96% CI, 1.8-3.6 months) for placebo (hazard ratio, 0.22 (96% CI, 0.13–0.36; P <.0001). Though not statistically significant, an objective response in the first 100 randomly assigned patients (primary endpoint) was achieved in 15% of those treated with cabozantinib vs 0% for placebo (P =.028).
“The FDA’s acceptance of our sNDA with Priority Review is an important step toward our goal of bringing Cabometyx to patients with previously treated radioactive iodine-refractory differentiated thyroid cancer,” said Michael M. Morrissey, PhD, Exelixis’ President and Chief Executive Officer. “Considering the lack of a standard of care in the treatment of this cancer following anti-VEGFR therapy, the progression-free survival benefit demonstrated in the phase 3 COSMIC-311 pivotal trial means Cabometyx, if approved, could become an important new treatment for these patients.”
A Prescription Drug User Fee Act target date for approval has been set for December 4, 2021.
- Exelixis announces US FDA accepts for Priority Review the supplemental New Drug Application for Cabometyx® (cabozantinib) for patients with previously treated radioactive iodine-refractory differentiated thyroid cancer. News release. August 5, 2021. https://www.businesswire.com/news/home/20210805005256/en/Exelixis-Announces-U.S.-FDA-Accepts-for-Priority-Review-the-Supplemental-New-Drug-Application-for-CABOMETYX%C2%AE-cabozantinib-for-Patients-with-Previously-Treated-Radioactive-Iodine-Refractory-Differentiated-Thyroid-Cancer.
- Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. Published online July 5, 2021. doi.org/10.1016/S1470-2045(21)00332-6.