This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined. After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated. The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976. BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

NCT01915576

Conditions

1. Neoplasms

Interventions

1. Drug: BAY1125976
2. Drug: BAY1125976
3. Drug: BAY1125976

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. --- E17K --- --- G49A ---

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. --- E17K --- --- G49A --- --- E17K --- --- G49A ---