Date: 2017-05-30
Type of information: Clinical research agreement
Compound: binimetinib with Opdivo® (nivolumab) and Opdivo® + Yervoy® (ipilimumab
Company: Array BioPharma (USA - CO) BMS (USA - NY)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism:
- kinase inhibitor/RAF kinase inhibitor/MEK (MAP kinase) inhibitor/monoclonal antibody/immune checkpoint inhibitor. The RAS/RAF/MEK/ERK pathway regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as non-small cell lung cancer, melanoma, colorectal, ovarian and thyroid cancers. Binimetinib is a small molecule MEK inhibitor and encorafenib is a small molecule BRAF inhibitor, both of which target key enzymes in this pathway. Array submitted a New Drug Application (NDA) for binimetinib in NRAS-mutant melanoma to the FDA at the end of June 2016. The FDA accepted the NDA with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017. Array BioPharma is the owner of binimetinib and encorafenib. Pierre Fabre licensed commercial rights to binimetinib and encorafenib for Europe and other global markets from Array in December 2015.
- Nivolumab is an 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. This monoclonal antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex.
- 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: metastatic colorectal cancer in patients with microsatellite stable tumors
Details:
- • On May 30, 2017, Array BioPharma and BMS announced the companies have entered into a clinical research collaboration to investigate the safety, tolerability and efficacy of Array's investigational MEK inhibitor, binimetinib in combination with Opdivo® (nivolumab) and Opdivo® + Yervoy® (ipilimumab) regimen as a potential treatment for metastatic colorectal cancer in patients with microsatellite stable tumors.
- The Phase 1/2 study is expected to establish recommended dose regimens for further study and explore the preliminary anti-tumor activity of combining binimetinib with Opdivo, as well as binimetinib in combination with the Opdivo + Yervoy regimen. Results from this first study, which is anticipated to begin in the second half of 2017, will be used to determine optimal approaches to further clinical development of these combinations.
- Binimetinib is being studied in clinical trials in advanced cancer patients, including the Phase 3 COLUMBUS trial in patients with BRAF-mutant melanoma and the Phase 3 BEACON CRC trial in patients with BRAF V600E-mutant colorectal cancer.
Financial terms: Under the terms of the agreement, Array and Bristol-Myers Squibb will jointly support the study with Array acting as the sponsor.
Latest news:
Is general: Yes
