Date: 2017-02-27
Type of information: Clinical research agreement
Compound: Cabometyx™ (cabozantinib) with Opdivo® (nivolumab) alone or in combination with Yervoy® (ipilimumab)
Company: BMS (USA - NY) Exelixis (USA - CA)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism:
- tyrosine kinase inhibitor/monoclonal antibody/immune checkpoint inhibitor . Cabozantinib is a kinase inhibitor that blocks abnormal kinase proteins involved in the development and growth of medullary cancer cells. Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGFRs and AXL. 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. In April 2015, cabozantinib received Fast Track designation by the FDA for the potential treatment of advanced renal cell carcinoma patients who have received one prior therapy. Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib.
- On April 25, 2016 Cabometyx™ was approved by the FDA for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
- Nivolumab is a fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Nivolumab is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes, thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. This monoclonal antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America.
- Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.
Disease: first-line renal cell carcinoma
Details:
- • On February 27, 2017, Exelixis and BMS announced the companies have entered into a clinical development collaboration to evaluate Cabometyx™ (cabozantinib), Exelixis’ small molecule inhibitor of receptor tyrosine kinases, with Opdivo® (nivolumab), BMS' PD-1 immune checkpoint inhibitor, either alone or in combination with Yervoy® (ipilimumab). The clinical development program, which will be co-funded by the companies, is expected to include a phase 3 pivotal trial in first-line renal cell carcinoma, with additional trials planned in bladder cancer, hepatocellular carcinoma (HCC), and potentially other tumor types.
- The clinical development collaboration builds upon previously published preclinical and clinical data that provide a scientific rationale for combining Cabometyx™ with immunotherapies, including phase 1 data of Cabometyx™ in combination with Opdivo® in patients with previously treated genitourinary tumors that were presented at the European Society for Medical Oncology (ESMO) 2016 Congress. Updated results from this part of the study as well as results from a second part evaluating the combination of Cabometyx™, Opdivo® and Yervoy® were presented during the poster discussion session (Abstract #293) on February 17 at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium, which was held in Orlando, Florida, February 16 – 18, 2017.
Financial terms:
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