FDA Foregoes Advisory Committee for Cabozantinib's Neuroendocrine Tumor Application
Key Insights
The FDA has canceled the Oncologic Drugs Advisory Committee meeting for Exelixis' cabozantinib sNDA, streamlining the review process.
The sNDA seeks approval for cabozantinib to treat advanced pancreatic and extra-pancreatic neuroendocrine tumors (search) in previously treated adults.
The FDA's decision is based on Phase III CABINET trial results, which showed significant progression-free survival improvements with cabozantinib.
Exelixis announced that the FDA will no longer convene an Oncologic Drugs Advisory Committee (ODAC) meeting to discuss the supplemental New Drug Application (sNDA) for cabozantinib (Cabometyx) in previously treated advanced pancreatic neuroendocrine tumors (search) (pNET (search)) and advanced extra-pancreatic neuroendocrine tumors (epNET (search)). The FDA is still reviewing the application, with a decision expected by the PDUFA date of April 3, 2025. This decision follows the submission of data from the Phase III CABINET trial, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with cabozantinib compared to placebo.
The sNDA is based on results from the Phase III CABINET trial, a study conducted by the National Cancer Institute's National Clinical Trials Network. The trial evaluated cabozantinib versus placebo in patients with advanced pNET (search) and epNET (search) who had received prior treatment. An independent Data and Safety Monitoring Board recommended stopping the trial early due to the substantial PFS benefit observed in the cabozantinib arm. The final results confirmed these improvements, establishing cabozantinib as a potential new treatment option for this patient population.
Clinical Significance of CABINET Trial
The CABINET trial's findings highlight a significant unmet need in the treatment of advanced neuroendocrine tumors (search). The study's primary endpoint was progression-free survival (PFS), assessed by blinded independent central review. Patients treated with cabozantinib experienced a statistically significant and clinically meaningful improvement in PFS compared to those receiving placebo. The study design allowed for crossover from the placebo arm to cabozantinib upon disease progression, further underscoring the potential benefit of the drug.
Cabozantinib's Existing Approvals
Cabozantinib, marketed as Cabometyx, is already approved for several indications, including advanced renal cell carcinoma (search) (RCC (search)) as a monotherapy and in combination with nivolumab as a first-line treatment. It is also approved for hepatocellular carcinoma (search) in patients previously treated with sorafenib, and for differentiated thyroid cancer (search) (DTC (search)) in adult and pediatric patients who have progressed following prior VEGFR (search)-targeted therapy and are radioactive iodine-refractory or ineligible. The potential approval for pNET (search) and epNET (search) would expand cabozantinib's utility in treating various advanced cancers.
Implications of FDA Decision
The FDA's decision to forego an advisory committee meeting suggests that the agency may view the data from the CABINET trial as sufficiently compelling to support approval. While the absence of an ODAC meeting does not guarantee approval, it can expedite the review process. The FDA's final decision, expected by April 3, 2025, will determine whether cabozantinib becomes a new standard of care for patients with previously treated advanced pNET (search) and epNET (search).