An Open-label, Phase I, Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1000394 Given in a 4 Week on / 2 Week Off Schedule in Subjects With Advanced Malignancies

Inclusion Criteria:

- Life expectancy of at least 12 weeks

- Subjects with advanced, histologically or cytologically confirmed solid tumors,
refractory to any standard therapy, have no standard therapy available, or subjects
must have actively refused any treatment which would be regarded standard, and / or
if in the judgment of the investigator, experimental treatment is clinically and
ethically acceptable

- At least 1 tumor lesion measurable by computer tomography (CT) scan or magnetic
resonance imaging (MRI) according to RECIST 1.1

- Estimated creatinine clearance 60 mL/min according to Modification of Diet in Renal
Disease Study Group (MDRD) formula(2)

- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the first dose of study drug

- Subjects with a history of hypertension should be on a stable anti-hypertensive
treatment for more than 7 days prior to the first dose of study drug

- Ability to understand and the willingness to sign a written informed consent. A
signed informed consent must be obtained prior to any study-specific procedures.

Exclusion Criteria:

- Any patient with potentially curable disease will be explicity excluded from
enrollment into the study

- Known hypersensitivity to the study drug (active investigational medicinal product or
excipients of the preparations) or any agent given in association with this study

- History of cardiac disease: congestive heart failure > NYHA Class II, unstable angina
(anginal symptoms at rest), new-onset angina (within the past 3 months prior to study
entry), myocardial infarction within the past 3 months prior to study entry, or
cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are
permitted)

- Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C(3)

- History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

- Symptomatic metastatic brain or meningeal tumors unless the subject is >3 months from
definitive therapy, has no evidence of tumor growth on an imaging study within 4
weeks prior to study entry, and is clinically stable with respect to the tumor at the
time of study entry. Subjects must not be on acute steroid therapy or taper off
steroid therapy (chronic steroid therapy is acceptable provided that the dose is
stable for 4 weeks prior to study entry and following screening CT / MRI scan).
Subjects with neurological symptoms should undergo a CT / MRI scan of the brain to
exclude new or progressive brain metastases. Spinal cord metastasis is acceptable

- Previous or coexisting cancer that is distinct in primary site or histology from the
cancer evaluated in this study EXCEPT cervical cancer in-situ, treated basal cell
carcinoma, superficial bladder tumors [Ta and Tis], or any cancer curatively treated
>3 years prior to study entry

- Anticancer chemotherapy or immunotherapy within 4 weeks of study entry. Mitomycin C
or nitrosoureas should not be given within 6 weeks of study entry. Anticancer
therapy is defined as any agent or combination of agents with clinically proven anti
tumor activity administered by any route with the purpose of affecting the
malignancy, either directly or indirectly, including palliative and therapeutic
endpoints. Accepted exceptions are bisphosphonates, Luteinizing hormone-releasing
hormone (LHRH) agonists for prostate cancer, and mitotane for adrenal carcinoma.

- Radiotherapy to target lesions within 3 weeks prior to the first dose of study drug.
Palliative radiotherapy will be allowed as described in Section 6.9 of this protocol.
Radiotherapy to the target lesions during study will be regarded as progressive
disease

- Use of biological response modifiers, such as granulocyte-colony stimulating factor
(G-CSF), within 3 weeks prior to the first dose of study drug. Granulocyte-colony
stimulating factor (G-CSF) and other hematopoietic growth factors may be used in the
management of acute toxicity such as febrile neutropenia when clinically indicated or
at the discretion of the investigator, however, they may not be substituted for a
required dose reduction