Ipsen expands collaboration and license agreement for development of Cabometyx® in advanced neuroendocrine tumors based on positive CABINET Phase III trial
- Decision adds to existing collaboration agreement with Exelixis, permitting Ipsen to seek potential marketing authorizations for Cabometyx® (cabozantinib) in advanced pancreatic and extra pancreatic neuroendocrine tumors outside of the U.S. and Japan
- Agreement based on CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology, which demonstrated improvements in progression-free survival for Cabometyx versus placebo 1
- Ipsen has engaged with regulatory authorities in the European Union and will submit a regulatory filing on the basis of these data
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).1
“With many people diagnosed with neuroendocrine tumors at an advanced stage of disease and treatment options limited upon progression, the need for efficacious new therapies is extensive,” said Christelle Huguet, EVP and Head of Research and Development, Ipsen. “The positive results demonstrated for Cabometyx within the CABINET Phase III trial represent clinically meaningful improvements in progression-free survival at a challenging stage of disease where there are few or no available treatment options. We look forward to discussing these clinical findings with regulatory authorities.”
Neuroendocrine tumors (NETs) are a group of uncommon tumors that develop in the cells of the neuroendocrine system throughout the body.2,3 The symptoms of NETs are often not distinct and difficult to identify, leading to delays in diagnosis, with 58% of people presenting with metastatic disease at diagnosis.3 The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.3,4 The survival rate varies greatly depending on the primary site and stage of disease, however for people living with advanced pNETs which has spread to distant parts of the body, the prognosis is poor, with a five-year survival rate of 23%.5
CABINET Phase III trial
Data from the study, which demonstrated PFS benefits at interim analyses, were presented at the European Society for Medical Oncology Congress 2023 by Professor Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute, Boston:1
- In the pNET cohort, at a median follow-up of 16.7 months, median PFS based on local radiology review was 11.4 months for Cabometyx versus 3.0 months for placebo (hazard ratio (HR) 0.27 [95% confidence interval (CI) 0.14-0.49] p<0.0001)1
- In the epNET cohort, at a median follow-up of 13.9 months, median PFS based on local radiology review was 8.3 months for Cabometyx versus 3.2 months for placebo (HR 0.45 [95% CI 0.30-0.66] p<0.0001)1
- The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were identified1
ENDS
About Cabometyx
Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).6 These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment.6,7,8,9
In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S.
In over 60 countries outside of the U.S. and Japan, including in the E.U., Cabometyx is currently indicated as a:7
- Monotherapy for advanced renal cell carcinoma (aRCC).
- as first-line treatment of adults with intermediate- or poor-risk disease.
- in adults following prior VEGFR-targeted therapy.
- In combination with nivolumab for the first-line treatment of aRCC in adults.
- Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy.
- Monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib.
The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC).
About neuroendocrine tumors
NETs are relatively uncommon and develop from cells of the neuroendocrine system; thus, can arise from a variety of locations throughout the body.2,3 The most common sites of NETs include the gastrointestinal (GI) tract, lungs and pancreas.2,10 Most NETs take years to develop and grow slowly, however some NETs can be fast-growing.2 The symptoms of NETs are often difficult to identify leading to patients being seen by multiple specialists and undergoing extensive testing before diagnosis is confirmed.3 As a result, almost a third of people take at least 5 years to be diagnosed with NETs.3 The five-year survival rate is dependent on the primary site of disease. For advanced GI-NET and lung NETs, where the cancer has spread to distant parts of the body, the five-year survival rates are 68% and 55%, respectively.11,12 For people diagnosed with advanced pNET, however, the prognosis is poor, with a five-year survival rate of 23%.5
About CABINET
CABINET (randomized, double-blinded Phase III trial 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.
The multicenter, Phase III CABINET pivotal trial enrolled a total of 290 patients in the U.S at the time of the interim analyses. Patients were randomized 2:1 to Cabometyx or placebo in two separate cohorts (pNET, n=93; epNET, n=197). The epNET cohort included patients with the following primary tumor sites: gastrointestinal tract, lung, unknown and other. 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. Food and Drug Administration-approved line of prior therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by retrospective independent central review. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with Cabometyx. Secondary endpoints included overall survival, radiographic response rate and safety. More information about this trial is available at ClinicalTrials.gov.
About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fuelled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries.
Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.
Ipsen contacts
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Media
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