– FDA approval based on the phase 3 CABINET pivotal trial, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus placebo –
– CABOMETYX is now the first and only systemic treatment that is FDA approved for previously treated neuroendocrine tumors regardless of primary tumor site, grade, somatostatin receptor expression and functional status –
– Exelixis is prepared to immediately support these new indications –
ALAMEDA, Calif.--(BUSINESS WIRE)--Mar. 26, 2025-- Exelixis, Inc. (Nasdaq: EXEL) today announced that the U.S. Food and Drug Administration (FDA) has approved CABOMETYX® (cabozantinib) for the treatment of 1) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET); and 2) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic NET (epNET). NET are heterogeneous tumors that arise from the neuroendocrine cells of the digestive tract and other organs, such as the lung and pancreas. Most patients with advanced disease face a poor prognosis.1,2,3,4
“The characteristics of NET vary widely from patient to patient, and very few treatment options have demonstrated the ability to improve outcomes across such a heterogeneous population,” said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “It was encouraging to see that cabozantinib resulted in significant delays in disease progression in the CABINET trial—regardless of primary tumor site and grade. This FDA approval marks a meaningful advancement, which may establish an important new treatment option for patients, without limitations based on somatostatin receptor expression and functional status.”
The FDA approval—adding to five previous approvals for CABOMETYX—is based on results from CABINET, a phase 3 pivotal trial evaluating CABOMETYX compared with placebo in two cohorts of patients with previously treated NET: advanced pNET and advanced epNET. Final progression-free survival results were presented at the 2024 European Society for Medical Oncology Congress and published in The New England Journal of Medicine. In January 2025, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors were updated to include cabozantinib as a category 1 preferred regimen for the majority of well-differentiated advanced NET following specific treatments, and as a category 2A preferred regimen for other forms of advanced NET, depending on tumor grade and different requirements for prior therapy.
“As a company committed to improving the standard of care for people living with advanced, difficult-to-treat cancers, we are proud to bring CABOMETYX to patients with previously treated advanced neuroendocrine tumors,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “I would like to extend our sincere gratitude to the Alliance for Clinical Trials in Oncology for conducting the CABINET trial, to the FDA for their collaboration on the review of this application and to all the patients and physicians who participated in this important study. Looking forward, we are doubling down on our commitment to the NET community as we prepare to initiate our STELLAR-311 pivotal trial examining zanzalintinib versus everolimus in the first half of 2025.”
The safety profile of CABOMETYX observed in each CABINET cohort was consistent with its known safety profile. No new safety signals were identified; however, the incidence of hypertension, regardless of treatment arm, was higher in NET patients compared to other approved tumor types. A majority of patients treated with CABOMETYX required dose modifications or reductions to manage adverse events.
"As a person who has lived with neuroendocrine tumors for over 14 years—and who has met many patients and caregivers in that time—I know that there are many challenges that come with this diagnosis, including the need to closely monitor the disease and adapt your treatment approach if faced with progression,” said Cindy Lovelace, co-founder of The Healing NET Foundation. “As very few targeted therapies have been approved for advanced NET in recent years, I am excited that CABOMETYX brings new hope to the patients in our community who have been in need of effective new treatment options.”
About CABINET (Alliance A021602)
CABINET (Randomized, Double-Blinded Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.
CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that had enrolled a total of 298 patients in the U.S at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in two separately powered cohorts (pNET, n=99; epNET, n=199). The epNET cohort included patients with the following primary tumor sites: gastrointestinal (GI) tract, lung, unknown primary sites and other organs. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.
About NET
NET are cancers that begin in the specialized cells of the body’s neuroendocrine system.1 These cells have traits of both hormone-producing endocrine cells and nerve cells.1 In 2024, the estimated prevalence of NET in the U.S. was more than 380,000 people.5 It is estimated that 161,000 to 192,000 people are living with unresectable, locally advanced or metastatic NET.5 The number of people diagnosed with NET has been increasing in recent decades.6 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing which may require focused treatment, while symptoms of non-functional NET are related primarily to tumor growth.7,8,9,10,11 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.12,13
NET can develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.1 The five-year survival rates for advanced GI and lung NET tumors are 68% and 55%, respectively.2,3 NET can also start in the pancreas, where they tend to be more aggressive, with a five-year survival rate of only 23% for advanced disease.1,4 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, molecular targeted therapy and peptide-receptor radionuclide therapy.14
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible; for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET); and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic NET (epNET). CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.
1 Neuroendocrine Tumors. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/22006-neuroendocrine-tumors-net. Accessed March 2025.
2 Survival Rates for Gastrointestinal Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html. Accessed March 2025.
3 Survival Rates for Lung Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html. Accessed March 2025.
4 Survival Rates for Pancreatic Neuroendocrine Tumor. ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html. Accessed March 2025.
5 Population Estimate: Unresectable, Locally Advanced or Metastatic Extra-Pancreatic NET. June 2024 (internal data on file).
6 Pathak, S., Starr, J.S., Halfdanarson T., et al. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab. September 2023;18(5):377-385.
7 Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®)–Patient Version. NCI website. Available at: https://www.cancer.gov/types/pancreatic/patient/pnet-treatment-pdq. Accessed March 2025.
8 What Is a Pancreatic Neuroendocrine Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/about/what-is-pnet.html. Accessed March 2025.
9 Carcinoid Syndrome. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/22103-carcinoid-syndrome. Accessed March 2025.
10 Signs and Symptoms of Gastrointestinal Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/signs-symptoms.html. Accessed March 2025.
11 Signs and Symptoms of Lung Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/signs-and-symptoms.html. Accessed March 2025.
12 McClellan, K., Chen. E.Y, Kardosh A., et al. Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors. Cancers. 2022;14(19):4769.
13 What is a Gastrointestinal Carcinoid Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/about/what-is-gastrointestinal-carcinoid.html. Accessed March 2025.
14 Neuroendocrine Tumor (NET). NCI website. Available at: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor. Accessed March 2025.