Exelixis Announces U.S. Food and Drug Administration (FDA) Accepted the Supplemental New Drug Application for Cabozantinib for Patients with Advanced Neuroendocrine Tumors
– The FDA assigned a Prescription Drug User Fee Act target action date of April 3, 2025 –
– Application is based on results from the phase 3 CABINET pivotal trial, in which cabozantinib provided a statistically significant and clinically meaningful improvement in progression-free survival versus placebo –
Exelixis, Inc. (Nasdaq: EXEL) today announced that its supplemental New Drug Application (sNDA) for cabozantinib (CABOMETYX®) has been accepted in the U.S. for: 1) the treatment of adults with previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated pancreatic neuroendocrine tumors (pNET), and 2) the treatment of adults with previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated extra-pancreatic NET (epNET).
“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, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “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 U.S. Food and Drug Administration (FDA) also granted orphan drug designation to cabozantinib for the treatment of pNET.
The FDA assigned a standard review with a Prescription Drug User Fee Act target action date of April 3, 2025.
I’ll keep you posted.
Read more here.
PARIS, FRANCE, 2 July 2024 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today confirmation of an expanded collaboration and license agreement with Exelixis, Inc. for the development of Cabometyx® (cabozantinib) in advanced pancreatic neuroendocrine tumors (pNETs) and advanced extra-pancreatic neuroendocrine tumors (epNETs). The agreement is based on positive outcomes from the CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology and sponsored by the National Cancer Institute (NCI), which investigated Cabometyx versus placebo in people living with advanced pNETs or advanced epNETs whose disease had progressed after prior systemic therapy. An independent Data and Safety Monitoring Board recommended to stop accrual to the study, unblind patients and allow crossover from placebo to Cabometyx. This was due to early efficacy demonstrated at an interim analysis in both of the trial’s cohorts, with clinically meaningful improvements in progression-free survival (PFS).
All will become clear, but these discussions may take up to a year in this type of scenario. I’ll keep you posted.
Read more here.
On August 24, 2023, Exelixis made an exciting announcement regarding the Phase 3 CABINET pivotal trial. This trial focused on evaluating the effectiveness of cabozantinib in treating advanced pancreatic and extra-pancreatic neuroendocrine tumors. The CABINET trial was a significant undertaking, involving multiple centers and enrolling a total of 290 patients who were divided into two groups.
The trial progressed smoothly, but to everyone’s surprise, it was stopped early. The reason for this premature conclusion was the remarkable improvement in efficacy observed. The Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board unanimously recommended ending the trial due to these unprecedented results.
“CABINET trial will be unblinded and stopped early due to a dramatic improvement in efficacy per a unanimous recommendation by The Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board”. Note: ‘Unblinded’ means that those receiving the placebo will now be able to be administered the actual trial drug.
What happens next?
All will become clear, but the trial sponsor will meet with FDA to discuss the data. One seasoned clinical trial source suggested these discussions may take up to a year in this type of scenario. I’ll keep you posted.
Read more here.
Cabozantinib is an oral drug which works by blocking the growth of new blood vessels that feed a tumour. In addition to blocking the formation of new blood cells in tumours, Cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other “anti-angiogenic” drugs. It is a type of drug called a growth blocker. Cabozantinib has been studied or is already in research studies as a possible treatment for various types of cancer, including prostate cancer, ovarian cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer.
Growth blockers are a type of targeted therapy and include tyrosine kinase inhibitors, proteasome inhibitors, mTOR inhibitors, PI3K inhibitors, histone deacetylase inhibitors and hedgehog pathway blockers. Cabozantinib is a tyrosine kinase inhibitor (TKI). They block chemical messengers (enzymes) called tyrosine kinases. Tyrosine kinases help to send growth signals in cells so blocking them stop the cell growing and dividing. Some TKIs can block more than one tyrosine kinase and these are known as multi-TKIs.
So Capozantinib is a targeted therapy and growth blocker just like Everolimus (Afinitor) and Sunitinib (Sutent). Very technical process but in the simplest of terms, Cabozantinib is designed to disrupt the actions of VEGF (a growth factor) and MET (a growth factor receptor) which promote spread of cancerous cells through the growth of new blood vessels. Whilst we are on this subject, please note Everolimus (Afinitor) is an mTOR inhibitor and Sunitinib (Sutent) is a tyrosine kinase inhibitor. Many people think these drugs are a type of chemo – that is incorrect, these are targeted therapies. See more on this by clicking here.
During my research, I found that it is an existing drug approval for other cancers and even has a connection to a type of Neuroendocrine Cancer called Medullary Thyroid Cancer (MTC). Cabozantinib, under the brand name of ‘Cometriq’ was approved by the FDA in 2012 for use in MTC which is frequently associated with Multiple Endocrine Neoplasia 2 (MEN2). Read more about Cometriq here. It’s also been approved by the FDA for advanced renal cell carcinoma (RCC) (branded as Cabometyx).
I also discovered that there is an exclusive licensing Agreement with the manufacturers (Elelixis) and Ipsen (of Lanreotide fame) to commercialize and develop Cabozantinib in regions outside the United States, Canada and Japan
The now suspended Phase III trial is entitled “Randomized, Double-Blinded Phase III Study of Cabozantinib Versus Placebo in Patients With Advanced Neuroendocrine Tumors After Progression on Prior Therapy (CABINET)”.
Sponsored by US’s National Institute of Health, the trial has around 435 locations across the US (see link below). The primary study (final data) was originally scheduled to complete Oct 2025 (but see breaking news above).
You can read the Phase 3 trial documentation by clicking here. This contains the eligibility criteria via the inclusion and exclusion criteria and the trial locations amongst many other things.
Yes, and they will have different sponsors and trial locations. Continue reading below.
A Phase 2 Study to Evaluate the Effects of Cabozantinib in Patients with Unresectable Metastatic Pheochromocytomas and Paragangliomas (only at MD Anderson Cancer Center Houston)
High-grade NENs are typically treated with platinum doublet chemotherapy; however, recurrences are inevitable and survival outcomes for patients with metastatic disease are dismal, underscoring the need for effective salvage treatment options. An ongoing hypothesis-generating phase 2 study (NCT04412629) is evaluating the efficacy and safety of the multitarget tyrosine kinase inhibitor cabozantinib in patients with high-grade NENs; the study design of this trial was presented at the 2020 North American Neuroendocrine Tumor Society Annual Symposium. This trial is based in Washington University School of Medicine Missouiri.
The eligibility criteria of the trial include patients with histologically confirmed high-grade, poorly differentiated NENs, excluding small-cell lung cancer, whose disease has progressed on first-line therapy; Eastern Cooperative Oncology Group performance status of 0 to 1; and Ki67 of ≥20% or mitotic count of >20 mitoses/high power field. Patients with transformed NENs, NENs of unknown origin, and mixed NENs were also eligible if a high-grade component is established. Eligible patients will receive oral cabozantinib at 60 mg daily on days 1 to 21 of a 21-day cycle.
The primary study end point is overall response rate; the secondary end points are safety, overall survival, and progression-free survival. Correlative studies for genetic and proteomic analysis will be performed using biopsy tissue acquired prior to cycle 2, as well as circulating tumor DNA from peripheral blood samples on day 1 of each cycle and on day 15 of cycle 1. Genetic analysis includes assessment of standard tumor markers, such as chromogranin, serotonin, urine 5-hydroxyindoleacetic acid, and specific hormones, dependent on the patient and investigator discretion. Whole-exome sequencing with copy number variant estimates of the initial biopsy (or optional start of treatment biopsy) will be performed.
See clinical trial document by clicking here. A small trial due to complete 31st July 2025.
Cabozantinib in High Grade Neuroendocrine Neoplasms – Full Text View – ClinicalTrials.gov
There is also another interesting trial involving Cabozantinib as a combo with Atezolizumab (Tecentriq). Atezolizumab is an immunotherapy or more specifically a monoclonal antibody and a type of immune checkpoint inhibitor. This trial is based in Spain and is due to complete Mar 2024.
The trial entitled: Exploratory Basket Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. CABATEN Study includes:
1. Well-differentiated neuroendocrine tumours of the lung and thymus (WHO grade 1 and 2, typical and atypical Lung NETs) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
2. Pheochromocytoma and paraganglioma after progression to peptide receptor radionuclide therapy (PRRT) if indicated. Prior chemotherapy and biological therapy, such as somatostatin analogs, are allowed.
3. Well-differentiated neuroendocrine tumours of digestive system (WHO grade 1 and 2) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
4. Grade 3 neuroendocrine neoplasm (WHO grade 3, including neuroendocrine (NET) and neuroendocrine carcinomas (NEC) G3) of any origin, excluding small cell lung cancer, after progression to chemotherapy or targeted agents/PRRT.
The clinical trial document can be found by clicking below:
Other trials listed in Clinical Trials dot Gov with Cabozantinib for various types of Neuroendocrine Neoplasm include (and apologies for the out-of-date term ‘carcinoid’ and the sometimes-inadequate search engine of the clinical trials database):
Click here but please note the Clinical Trials database is notoriously out of date (behind in changing things) and the filtering (tailored search) is notoriously inefficient”
I generated this blog article to add value rather than just post the outputs for your own perusal. I hope you find it useful.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net
The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.
Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional. Some content may be generated by AI which can sometimes be misinterpreted. Please check any references attached.
Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
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