Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGF receptors, AXL and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and maintenance of the tumor microenvironment.
Cabozantinib was discovered by Exelixis, and the company is focusing its development and commercialization efforts primarily on the compound in recognition of its potential to treat a wide variety of cancers. Cabozantinib’s global clinical development program includes approximately 45 ongoing or planned clinical trials, including: company-sponsored trials; studies conducted under the company’s Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP); and an Investigator-Sponsored Trial program.
Exclusive Licensing Agreement with Ipsen
In February 2016, Exelixis and Ipsen announced an exclusive licensing agreement for the commercialization and further development of cabozantinib. Under the agreement, Ipsen will have exclusive commercialization rights for current and potential future cabozantinib indications outside of the United States, Canada and Japan. The companies have agreed to collaborate on the development of cabozantinib for current and future potential indications as well. Exelixis maintains exclusive commercial rights for cabozantinib in the United States and Canada, and is continuing discussions to partner commercial rights in Japan.
For information on approved uses of cabozantinib, please visit our Medicines page.
Advanced Hepatocellular Carcinoma. Exelixis is also investigating cabozantinib in patients with advanced hepatocellular cancer (HCC) in CELESTIAL, a global, randomized, double-blind phase 3 pivotal trial. CELESTIAL is targeting an enrollment of 760 patients with advanced HCC who have received prior treatment with sorafenib. The primary endpoint of the trial is OS, and data are anticipated in the 2017 time frame. There is currently no standard of care available in second- or later-line patients who have received prior sorafenib, highlighting the unmet medical need in this disease setting. For more information on CELESTIAL, visit the trial’s page on ClinicalTrials.gov.
Research Sponsored by External Parties
Phase 1b Combination Trial with Immunotherapies. Exelixis’ collaborators at the National Cancer Institute are sponsoring a phase 1b trial of cabozantinib in combination with nivolumab alone, or in combination with nivolumab plus ipilimumab, in patients with genitourinary tumors, including bladder cancer and renal cell carcinoma (RCC). The primary endpoint of the trial is the determination of dose-limiting toxicities and a recommended phase 2 dose for the combinations. Exelixis believes that there is a strong rationale for combining cabozantinib with immunotherapies, including clinical evidence of cabozantinib’s ability to create a more immune-permissive environment, as well as preclinical data suggesting cabozantinib increases T-cell infiltration into tumors. Data from this trial could have relevance in other disease settings, including non-small cell lung cancer.
First-Line Intermediate or Poor Risk Renal Cell Carcinoma (CABOSUN). The company’s collaborators at the National Cancer Institute are also sponsoring CABOSUN, a randomized phase 2 trial comparing cabozantinib to sunitinib in first-line therapy of intermediate or poor risk patients per the standard risk classification. The primary endpoint of the trial is progression-free survival, and the study achieved its target enrollment of 150 patients in March 2015. Exelixis anticipates data in the first half of 2016. For more information on CABOSUN, visit the trial’s page on ClinicalTrials.gov.
Non-Small Cell Lung Cancer. At the American Society for Clinical Oncology’s 2015 Annual Meeting, investigators presented positive results from two clinical trials of cabozantinib in molecularly-defined subsets of non-small cell lung cancer.
- An investigator-sponsored phase 2 study in NSCLC patients with RET fusion genes met its primary endpoint and exceeded the predefined number of objective responses to declare success.
- A study sponsored by the National Cancer Institute evaluated cabozantinib, cabozantinib with erlotinib, and erlotinib monotherapy in a population of EGFR wild-type NSCLC patients. Results showed that the cabozantinib arm, and the combination arm of cabozantinib with erlotinib, significantly extended both PFS (the primary endpoint) and overall survival (a secondary endpoint), as compared to erlotinib on its own.
Exelixis is committed to working with its collaborators to explore further development of cabozantinib in NSCLC, including potential combination approaches with immunotherapy agents.
Additional Information on Cabozantinib’s Development
For more information on cabozantinib clinical trials, including additional trials conducted as part of our Investigator-Sponsored Trial program and collaboration with NCI-CTEP, please visit the Clinical Trials section of our site.
Cabozantinib is the subject of investigation in a variety of ongoing clinical trials; its safety and efficacy profile in these trials has not yet been established.