Prostatic Neoplasms
Conditions
Keywords
Phase I, Dose Escalation, Prostate cancer, Antibodies, Bispecific T-cell Engager (BiTE)
Brief summary
This is the first study where BAY2010112 is given to humans. Patients with castration resistant prostate cancer will be treated. Every patient will receive drug treatment, there is no placebo group. Patients will receive different dosages of BAY2010112 to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY2010112. The study will also assess the pharmacokinetics and the clinical efficacy of BAY2010112. BAY2010112 will be given daily as subcutaneous injection or as continuous intravenous infusion. 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.
Interventions
BIOLOGICALBAY2010112
Subcutaneous (s.c.) administration once daily. Starting dose will be 0.5 µg ; dose will be escalated dependent on any dose limiting toxicities
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Tumor response | Up to 2 years or longer if indicated | Tumor response is measured by measurable lesions |
| 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) | — |
| 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 |
Countries
Austria, Germany
Outcome results
None listed