BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC)

Inclusion criteria:

- The patient has histologically, or cytologically, confirmed adenocarcinoma of the
prostate.

- Male patient aged, equal to, or more than,18 years old.

- Patients with radiographic evidence of metastatic prostate cancer (stage M1 or D2).
Distant metastases evaluable by radionuclide bone scan, CT scan, or MRI within 28 days
before the start of study treatment.

- Patients with a prostate serum antigen (PSA), equal to, or more than, 5 ng/mL.

- Patients with prior surgical or chemical castration with a serum testosterone of <50
ng/mL. If the method of castration is luteinizing hormone releasing level hormone
(LHRH) agonists, the patient must be willing to continue the use of LHRH agonists
during protocol treatment.

- Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1 or 2.

- Cardiac left ventricular function with resting ejection fraction >50% as determined by
echocardiogram (ECHO) or multigated acquisition scan (MUGA).

- Absolute neutrophil count (ANC) >=1500/microlitre (uL).

- Haemoglobin >=9 g/dL.

- Platelets >=100,000/uL.

- Bilirubin <= 1.5 times the upper limit of normal (ULN).

- Aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 times the ULN(or <=
5 times the ULN if liver metastases are present).

- Creatinine <= 1.5 x ULN.

- International normalized ratio (INR) 5 seconds above the ULN (unless on oral anticoagulant therapy). Patients receiving
full dose anticoagulation therapy are eligible provided they meet all other criteria,
are on a stable dose of oral anticoagulant or low molecular weight heparin (except
warfarin or coumarin-like anticoagulants, which are not permitted).

- Fasting plasma glucose < 8.9 mmol/L (< 160 mg/dL) and HbA1c < 8.0%.

Inclusion criteria only for patients entering phase Ib escalation and phase II:

- Patients who have disease progression during, or after, receiving docetaxel and have
had at least 12 weeks of treatment and in the opinion of the investigator are unlikely
to derive significant benefit from additional docetaxel-based therapy, or were
intolerant to therapy with this agent.

- Patients who have disease progression during, or after, receiving abiraterone
treatment in any setting.

- Patients must have progressive disease defined as at least one of the following:

1. Progressive measurable disease: using conventional solid tumour criteria RECIST
1.1.

2. Bone scan progression: at least two new lesions on bone scan, plus a rising PSA
as described in (c) below.

3. Increasing PSA level: at least two consecutive rising PSA values over a reference
value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to
be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater
than PSA #2.

Inclusion criterion only for patients entering phase Ib expansion cohort:

- Patients must be receiving continuous enzalutamide treatment and show a rise in PSA
level: at least two consecutive rising PSA values over a reference value (PSA #1)
taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA
#2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2.

- Archive tumour tissue is available prior to recruitment for pharmacogenomic tests

Exclusion criteria:

- Prior therapy with agents targeting Insulin Growth Factor (IGF) and/or Insulin Growth
Factor Receptor (IGFR) pathway.

- Patients that have been treated with any of the following within 4 weeks of starting
trial treatment: chemotherapy, immunotherapy, biological therapies, molecular
targeted, hormone therapy (except LHRH agonists and LHRH antagonists), radiotherapy
(except in case of localized radiotherapy for analgesic purpose or for lytic lesions
at risk of fracture which can then be completed within 2 weeks prior to study
treatment).

- Use of any investigational drug within 4 weeks before start of trial treatment or
concomitantly with this trial.

- Patients that have been treated with strong cytochrome P450, family 2, subfamily C,
polypeptide 8 (CYP2C8) inhibitors, CYP2C8 inducers, within 2 weeks of starting the
trial treatment.

- Fridericia´s Corrected QT interval (QTcF) prolongation > 450 ms or QT prolongation
deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).
The QTcF will be calculated as the mean of the 3 ECGs taken at screening.

- Patients with small cell or neuroendocrine tumours.

- Patients with known or suspected leptomeningeal metastases.

- Uncontrolled or poorly controlled hypertension.

- Known human immunodeficiency virus infection or acquired immunodeficiency
syndrome-related illness.

- Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the
investigator.

- Patients unable to comply with the protocol as judged by the investigator.

- Active alcohol or active drug abuse as judged by the investigator.

- A history of allergy to human monoclonal antibodies.

- Patients who are sexually active and unwilling to use a medically acceptable method of
contraception, e.g. condom plus spermicide use for participating males, plus another
form of birth control such as implants, injectables, combined oral contraceptives,
intrauterine devices for female partners, during the trial and for at least three
months after end of active therapy. Men unwilling to agree to not donate sperm while
on trial drug and up to 6 months following the last dose of trial drug.

- Previous or concomitant malignancies at any other site with the exception of the
following:

- benign basal cell carcinoma

- benign low grade transitional cell carcinoma of the bladder

- other effectively treated malignancy that has been in remission for more than 5
years and is considered to be cured

- Only for patients entering phase Ib dose escalation and phase II cohorts:

- Patients who have received more than 2 prior non-docetaxel containing cytotoxic
chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer (mCRPC).

- Patients who have received a taxane based treatment or abiraterone, within 4 weeks
before start of study treatment.

- Patients that have received prior enzalutamide in any setting will not be eligible.

Exclusion criterion only for patients entering phase Ib expansion cohort:

- Patients that have received prior taxane-based chemotherapy or abiraterone in any setting
will not be eligible for the expansion cohort.

Additional exclusion criterion for patients undergoing tumour biopsy:

- For patients that are to undergo the tumour biopsy, a history of a hereditary bleeding
disorder, or clinically relevant major bleeding event in the past 6 months, as judged
by the investigator.

- Further exclusion criteria apply