First-in-man Dose Escalation Study of BAY2010112 in Patients With Prostate Cancer

Recruitment & Eligibility

Inclusion Criteria

Male subjects, aged >/= 18 years
Subjects with histologically or cytologically proven advanced castration-resistant prostate cancer (CRPC)
- who failed at least 1 taxane regimen and are refractory to abiraterone and/or enzalutamide therapy OR
- who have actively refused any treatment which would be regarded standard.
Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist.
Subjects must have shown progressive disease after discontinuation of anti-androgen therapy (i.e. flutamide, bicalutamide or nilutamide) before study drug treatment.
Total serum testosterone should be less than 50 ng/ml or 1.7 nmol/L
Evidence of progressive disease, defined as one or more (Prostate Cancer Working Group 2 (PCWG2) criteria):
PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
Nodal (in lymph nodes >/= 2cm) or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Appearance of one more new lesions in bone scan
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
Life expectancy of at least 3 months

Exclusion Criteria

Any anticancer therapy or immunotherapy within 4 weeks of start of first dose
Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
Prior radiotherapy (local palliative radiotherapy is permitted)
History of allergic reactions to monoclonal antibody therapy
History of clinical significant cardiac disease: including unstable angina, acute myocardial infarction within 6 months prior to first study treatment, congestive heart failure ≥New York Heart Association (NYHA) Class III), and arrhythmia requiring therapy except for beta-blockers, calcium channel blockers and digoxin or uncontrolled hypertension, despite optimal medical management
Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QT interval corrected for heart rate (QTc)-interval over 450 msec
Current evidence or history of uncured (i.a. any absolute risk of latent infection) of hepatitis B or C or human immunodeficiency virus (HIV) infection
Chronic systemic corticosteroid therapy or any other immunosuppressive therapies should have been stopped at screening start
Seizure disorder requiring therapy (such as steroids or anti-epileptics)
Subjects unable to inject the study drug subcutaneously for intended s.c. application
Non-suitable for a central venous access for intended c.i.v. administration

Study & Design

Arm && Interventions

Group	Intervention	Description
BAY2010112 (s.c.)	BAY2010112	-
BAY2010112 (c.i.v.)	BAY2010112	-

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse Events as a Measure of Safety and Tolerability	Up to 2 years or longer if indicated
Maximum Tolerated Dose (MTD)	Up to 2 years or longer if indicated	MTD is measured by adverse event profile at the end of Cycle 1. MTD will be the highest dose level achieved during dose escalation where the incidence of dose-limiting toxicities (DLTs) is below 20%

Secondary Outcome Measures

Name	Time	Method
Maximum drug concentration (Cmax) of BAY2010112 in serum after single and multiple doses administration	Cycle 1 Day1 and 15; (1 Cycle is 21 days long)
Area under the concentration versus time curve (AUC) from zero to infinity after single (first) and multiple doses of BAY2010112	Cycle 1 (1 Cycle is 21 days long)
Tumor response	Up to 2 years or longer if indicated	Tumor response is measured by measurable lesions
Prostate-specific antigen (PSA) response	Up to 2 years or longer if indicated	PSA response is measured by maximum decline in PSA that occurs at any point after treatment

Recruitment & Eligibility