A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy

Inclusion Criteria:

- No prior paclitaxel treatment for subjects in the dose escalation phase. MTD (maximum
tolerated dose) cohort expansion subjects may have had prior paclitaxel, but must not
have experienced moderate or severe hypersensitivity reactions to the drug.
Peripheral neuropathy must be Grade ≤ 1.

- No history of hypersensitivity (allergy) to drugs formulated in Cremophor EL
(polyoxyethylated castor oil), such as vitamin K, cyclosporin for injection
concentrate and teniposide for injection concentrate

- Histological or cytological documentation of non-hematologic malignant solid tumor,
excluding primary brain or spinal tumors. Patients with prior central nervous system
metastases are eligible if all of the following apply:

- Definitive treatment for all lesions (e.g. surgery, radiation) was completed at
least three months prior to enrollment

- All lesions must be stable or improving on MRI scan performed within one month
of enrollment

- All symptoms of the prior CNS metastases are stable

- At least one measurable lesion or evaluable disease, as per RECIST 1.1

- ECOG (eastern cooperative oncology group) Performance Status Assessment of 0 or 1

- Life expectancy of at least 12 weeks

- Serum creatinine ≤ 1.5 x ULN (upper limit of normal)

- Total bilirubin ≤ 1.5 x ULN

- Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver
involvement with cancer)

- Aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver
involvement with cancer)

- PT-INR/PTT (Prothrombin time-international normalized ratio / partial thromboplastin
time) < 1.5 x ULN (Subjects who are therapeutically anticoagulated with an agent such
as coumadin or heparin will be allowed to participate provided no other abnormalities
in the coagulation parameters exist). Low-dose aspirin is permitted (≤ 100 mg daily)

Exclusion Criteria:

- Medical and surgical history

- Prior paclitaxel treatment

- History of moderate to severe hypersensitivity (allergy) to drugs formulated in
Cremophor EL (polyoxyethylated castor oil), such as vitamin K, cyclosporin for
injection concentrate and teniposide for injection concentrate

- History of cardiac disease; congestive heart failure (CHF) > NYHA Class II;
active coronary artery disease, myocardial infarction within 6 months prior to
study entry; new onset angina within 3 months prior to study entry or unstable
angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy

- Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as
consistent fasting blood or plasma glucose > 125 mg/dL) or HgBA1c ≥ 7%

- Use of systemic corticosteroids within 2 days of the start of study treatment
(topical or inhaled steroids are permitted)

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

- Use of strong inhibitors of CYP3A4 (eg, ketoconazole, itraconazole,
clarithromycin, ritonavir, indinavir, nelfinavir, nefazodone and saquinavir) and
strong inducers of CYP3A4 (eg, rifampin) are not permitted from Day -14 of Cycle
1 and for the duration of the study

- Excluded therapies and medications for cancer

- Prior paclitaxel treatment (dose escalation patients only)

- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of
first study treatment. Hormonal therapy during the study or within 2 weeks of
first study treatment.

High dose chemotherapy with autologous stem cell rescue within 6 months prior to first
study treatment; or any high dose chemotherapy with allogeneic stem cell rescue.. Subjects
are also excluded if the autologous stem cell rescue has been done prior to 6 months, but
the investigator or sponsor feels that residual toxicities from these procedures will
increase the risk associated with study treatments Subjects must have recovered from the
acute toxic effects of the previous anti-cancer chemotherapy or immunotherapy (with the
exception of alopecia)

- Bisphosphonate therapy during the first 2 cycles of treatment