Exelixis Announces U.S. FDA Approval of CABOMETYX® (cabozantinib) for Patients with Previously Treated Advanced Neuroendocrine Tumors
Exelixis (NASDAQ: EXEL) has received FDA approval for CABOMETYX® (cabozantinib) to treat previously treated advanced neuroendocrine tumors (NET). The approval covers two specific indications: advanced pancreatic NET (pNET) and extra-pancreatic NET (epNET) in adults and pediatric patients 12 years and older.
The approval is based on the phase 3 CABINET trial results, which showed significant improvement in progression-free survival compared to placebo. CABOMETYX becomes the first and only FDA-approved systemic treatment for previously treated NET, regardless of primary tumor site, grade, somatostatin receptor expression, and functional status.
The National Comprehensive Cancer Network has updated its guidelines to include cabozantinib as a category 1 preferred regimen for well-differentiated advanced NET and category 2A for other forms. The safety profile was consistent with previous findings, though higher hypertension incidence was noted compared to other tumor types.
Exelixis (NASDAQ: EXEL) ha ricevuto l'approvazione della FDA per CABOMETYX® (cabozantinib) per il trattamento di tumori neuroendocrini avanzati (NET) precedentemente trattati. L'approvazione riguarda due indicazioni specifiche: NET pancreatico avanzato (pNET) e NET extra-pancreatico (epNET) in pazienti adulti e pediatrici di età pari o superiore a 12 anni.
L'approvazione si basa sui risultati dello studio di fase 3 CABINET, che ha mostrato un significativo miglioramento della sopravvivenza libera da progressione rispetto al placebo. CABOMETYX diventa il primo e unico trattamento sistemico approvato dalla FDA per NET precedentemente trattati, indipendentemente dal sito tumorale primario, dal grado, dall'espressione del recettore della somatostatina e dallo stato funzionale.
Il National Comprehensive Cancer Network ha aggiornato le proprie linee guida per includere cabozantinib come regime preferito di categoria 1 per NET avanzati ben differenziati e categoria 2A per altre forme. Il profilo di sicurezza è stato coerente con i risultati precedenti, sebbene sia stata notata una maggiore incidenza di ipertensione rispetto ad altri tipi di tumori.
Exelixis (NASDAQ: EXEL) ha recibido la aprobación de la FDA para CABOMETYX® (cabozantinib) para tratar tumores neuroendocrinos avanzados (NET) previamente tratados. La aprobación abarca dos indicaciones específicas: NET pancreático avanzado (pNET) y NET extra-pancreático (epNET) en pacientes adultos y pediátricos de 12 años o más.
La aprobación se basa en los resultados del ensayo de fase 3 CABINET, que mostró una mejora significativa en la supervivencia libre de progresión en comparación con el placebo. CABOMETYX se convierte en el primer y único tratamiento sistémico aprobado por la FDA para NET previamente tratados, sin importar el sitio del tumor primario, el grado, la expresión del receptor de somatostatina y el estado funcional.
La National Comprehensive Cancer Network ha actualizado sus pautas para incluir cabozantinib como un régimen preferido de categoría 1 para NET avanzados bien diferenciados y categoría 2A para otras formas. El perfil de seguridad fue consistente con hallazgos previos, aunque se observó una mayor incidencia de hipertensión en comparación con otros tipos de tumores.
Exelixis (NASDAQ: EXEL)는 CABOMETYX® (cabozantinib)에 대해 FDA 승인을 받았습니다. 이 약물은 이전에 치료받은 진행성 신경내분비 종양(NET)을 치료하는 데 사용됩니다. 승인은 두 가지 특정 적응증을 포함합니다: 성인 및 12세 이상의 소아 환자에서의 진행성 췌장 NET (pNET) 및 췌장 외 NET (epNET)입니다.
승인은 위약과 비교하여 무진행 생존율의 유의미한 개선을 보여준 3상 CABINET 시험 결과를 기반으로 합니다. CABOMETYX는 원발 종양 위치, 등급, 소마토스타틴 수용체 발현 및 기능적 상태에 관계없이 이전에 치료받은 NET에 대해 FDA에서 승인한 최초이자 유일한 전신 치료제가 됩니다.
National Comprehensive Cancer Network은 cabozantinib을 잘 분화된 진행성 NET에 대한 1군 선호 요법으로, 다른 형태에 대해서는 2A군으로 포함하도록 가이드라인을 업데이트했습니다. 안전성 프로필은 이전 연구 결과와 일치했지만, 다른 종양 유형에 비해 고혈압 발생률이 더 높다는 점이 주목되었습니다.
Exelixis (NASDAQ: EXEL) a reçu l'approbation de la FDA pour CABOMETYX® (cabozantinib) afin de traiter des tumeurs neuroendocrines avancées (NET) déjà traitées. L'approbation couvre deux indications spécifiques : NET pancréatique avancé (pNET) et NET extra-pancréatique (epNET) chez les adultes et les patients pédiatriques âgés de 12 ans et plus.
L'approbation est basée sur les résultats de l'essai de phase 3 CABINET, qui a montré une amélioration significative de la survie sans progression par rapport au placebo. CABOMETYX devient le premier et unique traitement systémique approuvé par la FDA pour les NET précédemment traités, quel que soit le site de la tumeur primaire, le grade, l'expression du récepteur de la somatostatine et l'état fonctionnel.
Le National Comprehensive Cancer Network a mis à jour ses directives pour inclure le cabozantinib comme un régime de catégorie 1 préféré pour les NET avancés bien différenciés et de catégorie 2A pour d'autres formes. Le profil de sécurité était cohérent avec les résultats précédents, bien qu'une incidence plus élevée d'hypertension ait été notée par rapport à d'autres types de tumeurs.
Exelixis (NASDAQ: EXEL) hat die FDA-Zulassung für CABOMETYX® (cabozantinib) erhalten, um zuvor behandelte fortgeschrittene neuroendokrine Tumoren (NET) zu behandeln. Die Zulassung umfasst zwei spezifische Indikationen: fortgeschrittenes pankreatisches NET (pNET) und extra-pankreatisches NET (epNET) bei Erwachsenen und pädiatrischen Patienten ab 12 Jahren.
Die Zulassung basiert auf den Ergebnissen der Phase-3-Studie CABINET, die eine signifikante Verbesserung des progressionsfreien Überlebens im Vergleich zu Placebo zeigte. CABOMETYX wird zur ersten und einzigen von der FDA zugelassenen systemischen Behandlung für zuvor behandelte NET, unabhängig vom primären Tumorstandort, Grad, Somatostatinrezeptorexpression und funktionalem Status.
Das National Comprehensive Cancer Network hat seine Richtlinien aktualisiert, um cabozantinib als bevorzugtes Regime der Kategorie 1 für gut differenzierte fortgeschrittene NET und Kategorie 2A für andere Formen aufzunehmen. Das Sicherheitsprofil war konsistent mit früheren Ergebnissen, obwohl eine höhere Inzidenz von Bluthochdruck im Vergleich zu anderen Tumorarten festgestellt wurde.
- First and only FDA-approved systemic treatment for previously treated NET across all tumor types
- Demonstrated significant improvement in progression-free survival vs placebo
- Received category 1 preferred regimen status from National Comprehensive Cancer Network
- Immediate commercial availability for new indications
- Expands CABOMETYX's approved indications to seven different uses
- Higher incidence of hypertension compared to other tumor types
- Majority of patients required dose modifications or reductions
- to second-line treatment only
Insights
The FDA approval of CABOMETYX for advanced neuroendocrine tumors (NET) represents a significant therapeutic advancement in an area with treatment options. The approval spans both pancreatic and extra-pancreatic NET subtypes, with no limitations based on primary tumor site, grade, receptor expression, or functional status - creating an unprecedented breadth of clinical application.
The CABINET trial data demonstrated statistically significant improvement in progression-free survival versus placebo, addressing a critical need for this heterogeneous and challenging disease group. Most advanced NET patients face poor prognoses with few effective therapies available. The National Comprehensive Cancer Network's swift guideline update to include cabozantinib as a category 1 preferred regimen - their highest recommendation level - underscores the clinical significance of these results.
While the safety profile showed manageable adverse events consistent with known data, the higher incidence of hypertension in NET patients compared to other approved indications warrants clinical attention. The requirement for dose modifications in most patients indicates careful monitoring will be necessary, typical for tyrosine kinase inhibitors in these populations.
This approval solidifies CABOMETYX's position as a versatile oncology agent, now with six FDA-approved indications. Exelixis's planned STELLAR-311 trial examining zanzalintinib versus everolimus demonstrates their strategic commitment to establishing dominance in the NET treatment landscape.
This FDA approval represents a substantial commercial opportunity for Exelixis, expanding CABOMETYX into an entirely new tumor type with competition. Being positioned as the "first and only" systemic treatment approved for previously treated NET regardless of several key parameters gives Exelixis significant market advantage and potential pricing power.
The NCCN's rapid guideline update to category 1 preferred status is particularly valuable, as it typically accelerates insurance coverage and physician adoption. This positions CABOMETYX ahead of competing therapies and could drive faster-than-expected uptake in clinical practice.
Strategically, this approval demonstrates Exelixis's successful execution of a label expansion strategy that maximizes return on their established asset. With six FDA approvals now for CABOMETYX, Exelixis continues to extract additional value from their flagship product while developing next-generation assets like zanzalintinib.
The company noted they are "prepared to immediately support these new indications," indicating their commercial infrastructure is ready without additional ramp-up costs. While market size specifics aren't provided, NET represents a meaningful revenue growth opportunity given the treatment landscape and CABOMETYX's unique approval across NET subtypes.
This approval strengthens Exelixis's oncology portfolio and reinforces their position as a growing mid-cap biopharma company successfully transitioning from single-product dependency to a more diversified pipeline approach.
– 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 –
“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
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
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
About CABOMETYX® (cabozantinib)
In the
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was
Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in
Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in
Diarrhea: CABOMETYX can cause diarrhea and it occurred in
Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in
Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in
Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in
Proteinuria: Proteinuria was observed in
Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <
Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in
Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in
Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.
Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.
ADVERSE REACTIONS
The most common (≥
CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.
CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
DRUG INTERACTIONS
Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.
Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.
Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
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.
Forward-Looking Statements
This press release contains forward-looking statements, including, without limitation, statements related to: the therapeutic potential of CABOMETYX for patients with previously treated advanced neuroendocrine tumors; Exelixis’ ability or plans to immediately support these new indications; Exelixis’ commitment to improving the standard of care for people living with advanced, difficult-to-treat cancers, including within the NET community; timing of plans to initiate the STELLAR-311 pivotal trial examining zanzalintinib versus everolimus; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the degree of market acceptance of CABOMETYX in the territories where it is approved and availability of coverage and reimbursement for this product; Exelixis’ ability to invest in the resources necessary to successfully commercialize CABOMETYX in the territories where it is approved and to execute its commercial strategy; Exelixis’ ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; Exelixis’ continuing compliance with applicable legal and regulatory requirements; Exelixis’ ability to protect its intellectual property rights; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of cabozantinib; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ other future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.
Exelixis, the Exelixis logo and CABOMETYX are registered
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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.
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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.
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