Sitravatinib (MGC D-0516) is a spectrum-selective kinase inhibitor which potently inhibits receptor tyrosine kinases (RTKs) including RET, TAM family receptors (TYRO3, Axl, MER), and split family receptors (VEGFR2, KIT). For more clinical trial information please visit CLINICALTRIALS.GOV.

Scientific Rationale

The receptor tyrosine kinases in the RET, CHR4q12, CBL, Trk, and DDR families are key regulators of signaling pathways leading to cell growth, survival and migration. RET, CHR4q12, CBL, Trk, and DDR are dysregulated in many cancers through overexpression or genetic alteration and act as oncogenic drivers promoting cancer development and progression. Collectively, the genetic alterations of the sitravatinib tyrosine kinase targets provide clinical development opportunities in multiple indications. Activating mutations and gene rearrangements of RET have been identified as oncogenic drivers in a subset of lung adenocarcinoma and were found to be mutually exclusive with other known driver alterations. Trk family kinases are also genetically altered in multiple cancers including gene rearrangements in lung adenocarcinoma and other solid tumors. In addition, activating oncogenic mutations involving DDR have been identified in lung cancer.

In Combination with Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is the first drug candidate produced from BeiGene’s immuno-oncology biologic programs. In a Phase 1 study, BeiGene is evaluating sitravatinib combined with tislelizumab in various solid tumors in China and Australia.