Clinical Trials /

Phase I Dose Escalation of Oral BAY1161909 in Combination With Intravenous Paclitaxel



Determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase II dose (RP2D) of BAY1161909 in combination with paclitaxel in subjects with advanced malignancies.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: Phase I Dose Escalation of Oral BAY1161909 in Combination With Intravenous Paclitaxel
  • Official Title: An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of Oral BAY1161909 in Combination With Weekly Intravenous Paclitaxel Given in an Intermittent Dosing Schedule in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 16804
  • NCT ID: NCT02138812


  • Medical Oncology


BAY1161909BAY1161909 + Paclitaxel
PaclitaxelBAY1161909 + Paclitaxel


Determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase II dose (RP2D) of BAY1161909 in combination with paclitaxel in subjects with advanced malignancies.

Detailed Description

      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

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

        -  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.

Trial Arms

BAY1161909 + PaclitaxelExperimentalParticipants received oral doses of BAY1161909 starting from 0.75 mg twice daily, from C1D1 onwards in a 2 days on/5 days off dosing schedule as single agent treatment in Cycle 1 (14 days), and from C2D8 onwards in a 2 days on/5 days off dosing schedule in combination with weekly intravenous paclitaxel on D1, D8, and D15 of the 28-day cycles. For single-dose Pharmacokinetic (PK) cohort: in Cycle 1, participants received a single oral dose of 6 mg BAY1161909 on C1D1 with no BAY1161909 dosing for the remainder of Cycle 1.
  • BAY1161909
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female subjects aged =/> 18 years

          -  Subjects with advanced, histologically or cytologically confirmed advanced
             malignancies (solid tumors), refractory to any standard therapy, have no standard
             therapy available, or subjects actively refused any standard treatment and / or if, in
             the judgment of the investigator, experimental treatment is clinically and ethically

          -  For the expansion cohort: women with histologically or cytologically confirmed triple
             negative breast cancer (TNBC)

          -  Subjects must have evaluable or measurable disease according to Response Evaluation
             Criteria In Solid Tumors (RECIST) 1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Life expectancy of at least 12 weeks

          -  Adequate bone marrow, liver, and renal functions

        Exclusion Criteria:

          -  Known hypersensitivity to the study drugs or excipients of the preparations or any
             agent given in association with this study

          -  Evidence of peripheral neuropathy of Grade > 2

          -  History of cardiac disease: congestive heart failure New York Heart Association (NYHA)
             class > II, unstable angina (anginal symptoms at rest), new-onset angina (within the
             past 3 months before study entry), myocardial infarction within the past 3 months
             before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta
             blockers, calcium channel blockers, and digoxin are permitted)

          -  Prior treatment with more than 3 lines of cytostatic therapies for metastatic disease
             unless specifically agreed between investigator and sponsor. Subjects with a history
             of any prior Grade =/> 3 toxicity associated with taxane treatment will be excluded.

          -  Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic
             blood pressure >90 mmHg, despite optimal medical management

          -  Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C

          -  History of human immunodeficiency virus (HIV) infection.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:Up to 2 years
Safety Issue:
Description:MTD is defined as the highest dose of oral BAY1161909 (administered in combination with or without IV paclitaxel) that can be given such that not more than 30% of the subjects experience a dose-limiting toxicity (DLT) during Cycles 1 and 2. The safety profile of oral BAY1161909 will first be determined in combination with 75 mg/m^2 IV paclitaxel [MTD (75)]. Starting in >Cohort 7 (12 mg 2 times daily [BID] BAY1161909) the MTD of oral BAY1161909 will then be refined for the combination with 90 mg/m^2 IV paclitaxel [MTD (90)].


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Bayer

Trial Keywords

  • Phase 1
  • Solid tumors
  • Breast cancer
  • Paclitaxel
  • Mps-1 inhibitor
  • Taxanes

Last Updated

October 12, 2018