BAY 1217389 + paclitaxel

BAY 1217389 + paclitaxel is a combination therapy consisting of BAY 1217389, an oral small molecule inhibitor of monopolar spindle 1 (MPS1) kinase, and paclitaxel, a well-established microtubule-interfering chemotherapeutic agent. MPS1 kinase plays a critical role in the spindle assembly checkpoint during mitosis; its inhibition drives tumor cells into mitosis despite DNA damage or chromosomal misattachment, leading to cell death through aneuploidy. Preclinical studies demonstrated that MPS1 inhibition can synergize with anti-mitotic agents like paclitaxel to enhance cancer cell killing. This combination was evaluated in phase I clinical trials for patients with advanced solid tumors and breast cancer. The main goal was to assess safety, determine the maximum tolerated dose (MTD), and evaluate pharmacokinetics. The combination showed considerable toxicity—primarily hematologic—and established the MTD for BAY 1217389 at 64 mg twice daily when combined with weekly paclitaxel[1][3][5][6]. Bayer developed both compounds.