Date: 2017-07-10
Type of
information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Exelixis (USA - CA) BMS (USA - NY)
Product: Cabometyx™ (cabozantinib) with Opdivo® (nivolumab) alone or in combination with Yervoy® (ipilimumab)
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: previously untreated, advanced or metastatic renal cell carcinoma
Therapeutic
area: Cancer - Oncology
Country: Argentina, Australia, Chile, Czechia, France, Germany, Mexico, Poland, Romania, Russian Federation, Turkey, USA
Trial
details: CheckMate 9ER is an open-label, randomized, multi-national phase 3 trial that aims to enroll approximately 1,014 patients with previously untreated advanced or metastatic renal cell carcinoma. Patients will be randomized 1:1:1 to one of three arms: Cabometyx™ and Opdivo®; Cabometyx™, Opdivo® and Yervoy®; or sunitinib. The primary efficacy analysis will compare the doublet combination versus sunitinib and the triplet combination versus sunitinib in intermediate/poor risk patients with renal cell carcinoma. (NCT03141177)
Latest
news:
- • On July 10, 2017, Exelixis and BMS announced the initiation of the phase 3 CheckMate 9ER trial to evaluate Opdivo® (nivolumab) in combination with Cabometyx™ (cabozantinib) tablets, a small molecule inhibitor of receptor tyrosine kinases, or Opdivo® and Yervoy® (ipilimumab) in combination with Cabometyx™ versus sunitinib in patients with previously untreated, advanced or metastatic renal cell carcinoma. The primary endpoint for the trial is progression-free survival (PFS).
Is
general: Yes
