FDA Accepts sNDA for Cabozantinib With 2 Neuroendocrine Tumor Indications

The drug also receives orphan drug designation for the treatment of pancreatic neuroendocrine tumors and a Prescription Drug User Fee Act target action date of April 3, 2025.

The FDA accepted a supplemental new drug application for cabozantinib for 2 indications: The treatment of previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated pancreatic neuroendocrine tumors (pNET) and extra-pancreatic NET (epNET). The drug also received orphan drug designation for the treatment of pNET as well as a Prescription Drug User Fee Act target action date of April 3, 2025.¹

Image Credit: Konstantin Yuganov - stock.adobe.com

“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,” Amy Peterson, MD, executive vice president of product development & medical affairs and chief medical officer at Exelixis, said in a news 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.”¹

The submission was based on final results from the phase 3 CABINET (NCT03375320) trial, which evaluated cabozantinib compared with the placebo in 2 cohorts. The cohorts included patients who were previously treated for NET or had advanced pNET or advanced epNET, according to the news release.¹

Cabozatinib, a tyrosine kinase inhibitor that could slow tumor growth, was compared to the placebo to determine efficacy for neuroendocrine or carcinoid tumors that may spread from origin to nearby tissue, lymph nodes, or distant parts of the body.²

In arm 1, individuals received oral cabozantinib once daily on days 1 through 28 of each cycle. Cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity. Arm 2 was similar, with patients receiving the placebo orally and once daily on days 1 through 28 of the cycle, repeating the cycle every 28 days. Patients had the ability to crossover to receive cabozantinib due to disease progression. All patients underwent computed tomography, magnetic resonance imaging, and/or x-ray imaging during screening and on study, according to the clinical trial information.²

Upon completion of study treatment, patients were followed up every 12 weeks until either disease progression or start of new anticancer therapy. Patients were also followed every 6 months until 8 years post-registration.²

About The Trial

Title: Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors

ClinicalTrials.gov ID: NCT03375320

Sponsor: National Cancer Institute

Completion Date (Estimated): March 2025

Primary objectives included whether cabozantinib significantly improved progression-free survival (PFS) compared to the placebo for those with NET that progressed after prior therapy and to determine PFS for patients with advanced carcinoid tumors that progressed after prior therapy. Secondary end points included improvement of OS for either cohort, the safety and tolerability of the drug in either cohort, and the overall radiographic response rate of the drug in either cohort.²

Investigators reported that the median PFS based on local radiology review was 11.4 months for cabozantinib compared with 3 months for the placebo for the pNET cohort, including a median follow-up of 16.7 months. In the epNET cohort, the median PFS was 8.3 and 3.2 months, respectively, with a median follow-up time of 13.9 months.³

The safety profile of cabozantinib was consistent with the known safety profile, with no new safety signals identified, according to the results.³

REFERENCES

1. Exelixis Announces US 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 6, 2024. https://www.businesswire.com/news/home/20240805262570/en/Exelixis-Announces-U.S.-Food-and-Drug-Administration-FDA-Accepted-the-Supplemental-New-Drug-Application-for-Cabozantinib-for-Patients-with-Advanced-Neuroendocrine-Tumors

2. Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors. ClinicalTrials.gov identification: NCT03375320. Updated July 3, 2024. Accessed August 6, 2024. https://clinicaltrials.gov/study/NCT03375320

3. 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 6, 2024. https://ir.exelixis.com/news-releases/news-release-details/detailed-results-phase-3-cabinet-pivotal-trial-evaluating