BAY1161909 is a potent and highly selective inhibitor of monopolar spindle 1 (Mps1) kinase
      activity. Human Mps1 is a serine threonine kinase which functions as a core component of the
      spindle assembly checkpoint (SAC), a key surveillance mechanism that monitors the attachment
      of spindle microtubules to the kinetochores of the chromosomes during pro-metaphase and halts
      the transitions to anaphase until all chromosomes are bi-oriented, fully attached, and
      correctly tensed at the metaphase plate. Mps1 is expressed in the mitosis phase of the cell
      cycle in proliferating cells. Overexpression of Mps1 has been observed in several cancer cell
      lines and tumor types including lung and breast cancers.

      Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the
      SAC either by destabilizing or stabilizing spindle microtubules resulting in mitotic arrest.
      Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or
      into a mitotic catastrophe leading to cell death. In contrast, Mps1 inhibitors inactivate the
      SAC and accelerate progression of cells through mitosis eventually resulting in severe
      chromosomal missegregation, mitotic catastrophe, and cell death. Consequently, Mps1
      inhibition leads to failure of cells to arrest in mitosis in response to anti-mitotic drugs.
      Thus, the combination of microtubule-interfering agents and Mps1 inhibition strongly
      increases chromosomal segregation errors and cell death and therefore, constitutes an
      efficient strategy for selectively eliminating tumor cells.

      This study will attempt to answer the following questions:

        -  What are the side effects of BAY1161909 when given at different dose levels and
           schedules with paclitaxel?

        -  What dose level and schedule of BAY1161909 should be tested in future clinical research
           studies?

        -  How much BAY1161909 and paclitaxel is in the blood at specific times after
           administration?

        -  Does the treatment with BAY1161909 with paclitaxel show any effect on the tumor growth?

        -  Are there specific biomarkers that might be able to explain why some patients respond to
           treatment and others do not.