Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients

Inclusion Criteria:

- For dose escalation cohorts: Subjects with advanced, histologically or cytologically
confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory
to standard treatment with no standard therapy available, or subjects actively refuse
any treatment, which would be regarded standard. In addition, the investigator must
judge the experimental treatment as clinically and ethically acceptable

- For expansion cohort only: Subjects with histologically or cytologically proven
metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects
with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least
one line of chemotherapy in the metastatic setting and not amenable to surgery with
curative intent

- Subjects must have measurable disease (Response evaluation criteria in solid tumors
(RECIST 1.1)

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2

- Bone marrow, liver and renal functions as assessed by adequate laboratory methods to
be conducted within 7 days prior to starting study treatment

- Subjects must provide tumor biopsies before treatment

- Recovery to CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade
0 or Grade 1 or recovery to baseline preceding the prior treatment of any previous
drug / procedure-related toxicity (except alopecia, anemia, and hypothyroidism)

Exclusion Criteria:

- History of cardiac disease including congestive heart failure > New York Heart
Association (NYHA) Class II

- Subjects with type 1 or type 2 diabetes mellitus

- Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated
hemoglobin (HbA1c) ≥ 7%

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

- Active infections of CTCAE (Common Terminology Criteria for Adverse Events Version
4.03) Grade >2 or infections of CTCAE Grade 2 not responding to therapy

- Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months
from definitive therapy, has a negative imaging study within 4 weeks of study entry
and is clinically stable with respect to the tumor at the time of study entry.

- Subjects undergoing renal dialysis

- Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study except cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively
treated > 3 years prior to study entry

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

- Treatment with oral steroids (dose ≥ 10 mg/day of methylprednisolone or equivalent)

- Clinically relevant findings in the ECG such as a second- or third-degree AV block,
prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msec

- Acute toxic effects of previous anticancer chemotherapy or immunotherapy have to be
normalized to CTCAE Grade equal or lower than 1 (excluding alopecia)