FDA Accepts Cabozantinib Application in Advanced Neuroendocrine Tumors

Microscopic, photorealistic image of neuroendocrine tumor cells - Generated with Google Gemini AI

• The FDA has accepted the filing of a supplemental new drug application (sNDA) of cabozantinib (Cabometyx) for the treatment of neuroendocrine tumors (NETs).
• A Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025, has been set.
• The filing is supported by the phase 3 CABINET study (NCT03375320).

The filing of the sNDA for cabozantinib, a tyrosine kinase inhibitor, in NETs has been accepted by the FDA, and a PDUFA target action date of April 3, 2025, has been set.¹

Specifically, the sNDA covers cabozantinib for the the treatment of adults with previously treated, locally advanced/unresectable or metastatic, well or moderately differentiated pancreatic NETs (pNETs) and previously treated, locally advanced/unresectable or metastatic, well or moderately differentiated extrapancreatic NETs (epNETs).

“The FDA’s acceptance of this application marks another important milestone in our commitment to bringing cabozantinib to patients living with difficult-to-treat cancers and who have limited treatment options,” said Amy Peterson, MD, executive vice president of product development and medical affairs and chief medical officer at Exelixis, in a press release. “We appreciate the opportunity to work with the FDA in the coming months as they review our application, with the goal to bring this new, effective treatment option to patients with advanced neuroendocrine tumors as quickly as possible.”

The sNDA is supported by findings from the phase 3 CABINET study, which was stopped early due to compelling activity. Initial results were presented at the 2023 European Society for Medical Oncology (ESMO) Congress. Final results are expected to be presented at this year’s ESMO Congress.

In patients with pNETs, cabozantinib led to a median progression-free survival (PFS) of 11.4 months vs 3.0 months with placebo (HR, 0.27; 95% CI, 0.14-0.49; P <.0001). In patients with epNETs, the median PFS was 8.3 months with cabozantinib vs 3.2 months with placebo (HR, 0.45; 95% CI, 0.30-0.66; P <.0001). The safety profile of cabozantinib was consistent with previous reports, and no new safety signals were identified.^2,3

“There’s an unmet need for new treatment options for patients with advanced NETs,” Jennifer A. Chan, MD, MPH, clinical director of the Gastrointestinal Cancer Center and director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute in Boston, Massachusetts, and associate professor of medicine at Harvard Medical School, said during the presentation of the data.³ “Multiple studies have shown that VEGF pathway inhibitors are active against NETs.”

About the Phase 3 CABINET Study

The phase 3 CABINET study enrolled 296 patients across 436 locations with pNETs or epNETs.⁴ PFS is the study’s primary end point, and secondary end points include overall survival, incidence of adverse events, and radiographic response rate.

Patients were randomized to receive cabozantinib or placebo daily in 28-day cycles until disease progression or unacceptable toxicity occurred.

To be eligible for enrollment in the study, patients had to experience disease progression following at least 1 line of FDA-approved therapy.

REFERENCES:

1. Exelixis announces U.S. Food and Drug Administration (FDA) accepted the supplemental new drug application for cabozantinib for patients with advanced neuroendocrine tumors. News release. Exelixis, Inc. August 6, 2024. Accessed August 7, 2024. https://tinyurl.com/y83rxbz3

2. Detailed results from phase 3 CABINET pivotal trial evaluating cabozantinib in advanced neuroendocrine tumors presented at ESMO 2023. News release. Exelixis, Inc. October 22, 2023. Accessed August 7, 2024. https://tinyurl.com/32a9kx4h

3. Chan J, Geyer S, Ou FS, et al. Alliance A021602: Phase III, double-blinded study of cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET). Ann Oncol. 2023;34(suppl 2):S192. doi:10.1016/j.annonc.2023.10.047

4. Testing cabozantinib in patients with advanced pancreatic neuroendocrine and carcinoid tumors. ClinicalTrials.gov. Updated July 3, 2024. Accessed August 7, 2024. https://www.clinicaltrials.gov/study/NCT03375320