Phase 3 Trial Update of Cabozantinib for Medullary Thyroid Cancer

Exelixis released data from a Phase 3 trial of cabozantinib in patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC).

The EXAM trial was an international, randomized, placebo-controlled, double-blinded trial. It enrolled 330 patients with locally advanced or metastatic MTC that had progressed per RECIST within 14 months of screening. Patients were randomized 2:1 to cabozantinib (N=219) or placebo (N=111).

The trial, known as EXAM, met its primary endpoint of improving progression-free survival (PFS), with patients in the cabozantinib arm achieving a median PFS of 11.2 months compared with 4 months for patients in the placebo arm. Cabozantinib’s benefit on PFS was seen across a number of pre-specified subgroups including RET mutational status or prior tyrosine kinase inhibitor (TKI) therapy. Overall response rate (ORR), a secondary endpoint, was 28% in the cabozantinib arm and 0% in the placebo arm. Estimated PFS at one year was 47.3% with cabozantinib vs. only 7.2% with placebo. Exelixis recently submitted a New Drug Application (NDA) for cabozantinib in MTC to the FDA.

Cabozantinib is a MET, VEGFR2, and RET inhibitor. MET is up-regulated in many tumor types and promotes tumor cell survival, invasion and metastasis. Further up-regulation of MET occurs under hypoxic conditions, which are often exacerbated by VEGF-pathway inhibitors, promoting increased tumor cell invasion and metastases. Activation of RET is a frequent occurrence in both medullary and papillary thyroid cancers. Cabozantinib blocks metastasis and angiogenesis to kill tumor cells.

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