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.”


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A Prescription Drug User Fee Act target date for approval has been set for December 4, 2021.

Cabometyx is currently indicated for advanced renal cell carcinoma and hepatocellular carcinoma.

References

  1. 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.
  2. 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.