Exelixis, Inc. (NYSE: Exelixis) today announced that the U.S. Food and Drug Administration (FDA) has approved Cabometyx (Cabozantinib) for the treatment of patients with previously treated radioiodine-refractory differentiated thyroid cancer (DTC). Specifically, pediatric and adult patients with locally advanced or metastatic DTC who were ≥12 years of age, progressed after prior treatment with vascular endothelial growth factor receptor (VEGFR-targeted therapy), refractory to radioactive iodine (if applicable), or not eligible for radioactive iodine therapy. The FDA has previously granted Breakthrough Therapy Designation (BTD) and priority Review to Cabometyx, more than 2 months ahead of the Prescription Drug User Fee Act (PDUFA) target action date of December 4, 2021.
DTC is the most common type of thyroid cancer in the United States. DTC patients who progress after prior treatment and are resistant to radioactive iodine therapy usually have a poor prognosis and limited treatment options. Cabometyx will bring new hope to these DTC patients. Data from the Pivotal Phase 3 COSMIC-311 trial showed that Cabometyx treatment significantly extended progression-free survival (PFS) compared to placebo.
Dr. Marcia S. Brose, principal investigator of the COSMIC-311 trial and co-director of community Clinical Trials at Sidney Kimmel Cancer Center at Thomas Jefferson University in the United States, said: "Prior to today, patients with refractory radioactive iodine DTC who progressed after VEGFR-targeted therapy faced aggressive disease with no standard treatment options. In cosmIC-311 Pivotal Phase 3 trial, Cabometyx extended survival time in patients without cancer progression. "The FDA's approval of Cabometyx is a significant step forward for these patients who are in urgent need of a new treatment option."
This approval is based on results from the Pivotal Phase 3 COSMIC-311 trial. This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial in patients with disease progression following prior treatment with two vascular endothelial growth factor receptor (VEGFR) targeted therapies. The study enrolled about 300 patients at 150 sites worldwide. In the study, patients were randomized in a 2:1 ratio to receive either Cabometyx 60 mg orally once daily or placebo. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR).
In a planned interim analysis, Cabometyx treatment significantly reduced the risk of disease progression or death by 78% compared with placebo in an intentional-treatment (ITT) population (HR=0.22; 96% CI: 0.15 0.31; P < 0.0001). The median follow-up was 10.1 months, with a median PFS of 11.0 months (n=170) in the Cabometyx group and only 1.9 months (n=88) in the placebo group, as assessed by the blind Independent Radiological Review Board. The safety in this study is consistent with the previously observed safety of Cabometyx.
Thyroid cancer can be differentiated, medullary and anaplastic. Differentiated thyroid cancer, which accounts for 90% of all cases, is usually treated with surgery followed by radioiodine ablation to remove the remaining thyroid tissue, but about 5% to 15% of patients are resistant to radioiodine therapy. For these patients, life expectancy is only 3-5 years from the discovery of metastatic lesions.
The active ingredient of Cabometyx is Cabozantinib, a tyrosine kinase inhibitor (TKI) that plays an anti-tumor role by targeting the MET, VEGFR2 and RET signaling pathways, killing tumor cells, reducing metastasis and inhibiting angiogenesis. In the United States and the European Union, Cabometyx is approved for the treatment of patients with advanced renal cell carcinoma (RCC) and patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.
