Exelixis, an innovative leader in oncology striving to revolutionize cancer care with next-gen therapies, recently announced that the United States Food and Drug Administration (FDA) has confirmed their supplemental New Drug Application (sNDA) for Cabozantinib (Cabometyx) will be reviewed at the Oncologic Drugs Advisory Committee (ODAC) meeting planned for March 2025. This pertains to its use in adults with prior treatments for advanced pancreatic neuroendocrine tumors (pNET) and advanced extra-pancreatic NET (epNET).
This sNDA is founded on the consequential outcomes of the phase 3 CABINET trial, orchestrated under the National Cancer Institute’s National Clinical Trials Network. The study scrutinized cabozantinib against a placebo for pNET and epNET cases. By August 2024, Exelixis disclosed that the FDA recognized cabozantinib with an orphan drug status for pNET management, with an action date per the Prescription Drug User Fee Act set for April 3, 2025.
In August 2023, it was revealed that the Alliance for Clinical Trials in Oncology’s Data and Safety Monitoring Board advised halting trial enrollment and allowing patient crossover from placebo to cabozantinib within the CABINET trial due to marked improvements in progression-free survival at initial analysis.
Ultimately, the 2024 European Society of Medical Oncology Congress showcased the final trial results, which were simultaneously published in the New England Journal of Medicine, reinforcing statistically significant enhancements in progression-free survival for cabozantinib versus placebo. These findings were consistent across various clinical subgroups, including tumor origin, grade, and prior systemic therapies.
CABINET is structured as a multicenter, double-blinded, placebo-controlled phase 3 study involving 298 US patients. Participants were randomized in a 2:1 ratio to receive either cabozantinib (60 mg) or a placebo across distinct cohorts (pNET, n=95; epNET, n=203). The epNET cohort involved diverse primary tumor sites, iteratively evaluated under a separate statistical framework. Eligibility mandated measurable disease per RECIST 1.1 criteria with progression post previous FDA-sanctioned systemic therapy. Primary and secondary endpoints analyzed progression-free survival, overall survival, response rates, and safety.
Currently, in the US, Cabometyx tablets are approved for advanced renal cell carcinoma (RCC), either as a solo treatment or combined with nivolumab as a primary RCC therapy. Additionally, it’s for hepatocellular carcinoma resistant to sorafenib, and adult/pediatric metastatic differentiated thyroid cancer post-VEGFR-targeted therapy. Cabozantinib has gained approval in over 65 countries outside the US, except Japan. Exelixis has partnerships with Ipsen Pharma SAS for global (except Japan) commercialization and Takeda Pharmaceutical for Japanese market development. Exelixis still holds exclusive rights in the US.
Neuroendocrine tumors (NETs) originate from the body’s neuroendocrine cells, possessing combined endocrine and neural attributes. In the US alone, estimates suggest 161,000 to 192,000 individuals face unresectable, advanced, or metastasized NETs, with diagnosis rates rising. Functional NETs emit peptide hormones causing severe symptoms such as diarrhea and hypertension, while non-functional NETs lead primarily to tumor growth-related issues. Although NETs often grow slowly, advanced stages invariably lead to complex progression and refractory scenarios.
Neuroendocrine tumors can arise anywhere in the body, predominantly occurring in the GI tract or lungs, previously categorized as carcinoid tumors, and recently termed epNET. Five-year survival rates for advanced GI and lung NETs stand at 68% and 55%, respectively. In contrast, pancreatic NETs exhibit aggressive traits, with a significantly lower five-year survival rate of 23% for advanced cases. Available treatments for progressing NETs encompass somatostatin analogs, chemotherapy, targeted therapies, and peptide-receptor radionuclide therapy.