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

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