BAY1238097, First in Man

Inclusion Criteria:

- Subjects with advanced, histologically or cytologically confirmed tumor, refractory
to any standard treatment, with no standard therapy available, in whom standard
therapy is not a therapeutic option or the subject actively refuses use of
chemotherapy which would be regarded standard and/or if in the judgment of the
investigator, experimental treatment is clinically and ethically acceptable.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Life expectancy of at least 12 weeks

- Adequate liver and renal functions as assessed by the following laboratory
requirements to be conducted within 7 days prior to starting study treatment:

- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5
x ULN for subjects with hepatic involvement with tumor)

- Amylase and lipase ≤ 2.5 x ULN (≤ 5 x ULN for subjects with pancreas involvement with
tumor)

- Prothrombin time (PT-INR)/ partial thromboplastin time (PTT) ≤ 1.5 x ULN. Subjects
who are therapeutically treated with an agent such as warfarin or heparin will be
allowed to participate provided that no prior evidence of underlying abnormality in
coagulation parameters exists. Close monitoring of at least weekly evaluations will
be performed until INR is stable based on a measurement that is pre dose as defined
by the local standard of care

- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min per 1.73 m2 according to the
Modification of Diet in Renal Disease Study Group (MDRD) formula (see Section 14.6)

- Adequate cardiac function (left ventricular ejection fraction [LVEF] ≥50% measured by
echocardiography or multi-gated acquisition [MUGA] scan)

Exclusion Criteria:

- History of cardiac disease including congestive heart failure New York Heart
Association (NYHA) Class >II (Section 14.7), unstable angina (anginal symptoms at
rest) or new-onset angina (within the last 6 months) or myocardial infarction within
the past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy except
for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (eg
angina pectoris, myocardial infarction within 6 months prior to study entry, major
regional wall motion abnormalities upon baseline echocardiography)

- Moderate and severe hepatic impairment, ie Child-Pugh B or C

- Restrictive lung diseases due to parenchymal damage (eg idiopathic lung fibrosis) or
pleural adhesions. Patients with lung resection, scoliosis or thorax malformations
can be included provided adequate spirometry testing during screening (eg FEV-Forced
expiratory volume 1 ≥ 70%; age, sex and height adapted vital capacity)

- Evidence or history of bleeding diathesis. Any hemorrhage/bleeding event ≥ CTCAE
(Common terminology criteria for adverse events) Grade 3 within 4 weeks of first dose
of study drug

- Human immunodeficiency virus (HIV) infection

- Chronic or active hepatitis B or C (patients positive for HBsAg or HBcAb will be
eligible if they are negative for HBV-DNA; patients positive for HCVAb will be
eligible if negative for HCV-RNA)

- History of other malignancy which could affect compliance with the protocol or
interpretation of results. Patients with a history of curatively treated non-melanoma
skin cancer or in situ carcinoma of the cervix or breast are allowed. Patients with a
malignancy that has been treated with curative intent will also be allowed if the
malignancy has been in complete remission without treatment for at least 1 year prior
to Cycle 1 Day 1 of study treatment. A recent history of myelodysplastic syndrome in
patients with secondary leukemia is allowed

- Autologous bone marrow transplant or stem cell rescue within 4 months of study entry

- Any condition that is unstable or could jeopardize the safety of the patient and
his/her compliance in the study

- Anticancer chemotherapy or immunotherapy during the study or within less than 3
half-lives for anticancer chemotherapy or 6 weeks for antibody therapies (2 weeks for
leukemia patients) prior to start of study drug.

- Use of any strong CYP3A4 inhibitor such as ketoconazole, itraconazole,
clarithromycin, ritonavir, indinavir, nelfinavir, or saquinavir (see Table 6 6) 14
days before the first dose of study drug or during the study

- Use of any strong CYP3A4 inducer such as rifampin, St John's Wort, or other herbal
preparations that contain any strong CYP3A4 inducer (see Table 6 6) 14 days before
the first dose of study drug or during the study

- Clinically relevant findings in the ECG such as a second-degree or third-degree
atrioventricular (AV) block (subjects with AV block and pacemaker in place for >1
year and checked by a cardiologist within ≤6 months before the first dose of study
drug will not be excluded), prolongation of the QRS complex over 120 msec or of the
QTc interval (Fridericia, QTcF) over 470 msec (subjects with a pacemaker and QRS
interval over 120 msec or QTc inverval over 470 msec may be enrolled on a
case-by-case basis, following a discussion between the investigator and the sponsor).