Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer

Inclusion criteria:

• Male 18 years and older.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Presence of skeletal, or soft-tissue/visceral/nodal metastases according to one of thefollowing criteria:
• Confirmed pathological fracture related to the disease OR
• Confirmation of distant bone and/or soft-tissue and/or visceral metastases on CTor MRI scan or bone scintigraphy OR
• Positive pathology report of metastatic lesion
• Disease progression despite androgen-deprivation therapy (ADT) as indicated by:
• Prostate-specific antigen (PSA) increase that is ≥ 2 ng/mL and ≥ 25% above theminimum PSA as reached during ADT or above the pre-treatment level, if noresponse was observed and which is confirmed by a second value 1 or more weekslater OR
• Progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesionmeasurable per RECIST v1.1 criteria, confirmation by an independent reviewfacility (IRF) required OR
• Two or more new lesions appearing on bone scan/imaging compared with a previousscan (confirmation by IRF required)
• Maintenance of castrate conditions: patients, who have not had a surgical orchiectomy,must continue with hormone therapy with gonadotropin releasing hormone/ luteinizinghormone-releasing hormone (GnRH/LHRH) agonists or antagonists to reach levels of serumtestosterone of ≤ 1.7 nmol/L (50 ng/dL). The duration of the castration period must beat least 4 months before screening as evidenced by combination of clinical/laboratorydata (see section 6.8.1).
• Laboratory criteria:
• White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L)
• Neutrophil count greater than 1,500/mm3 (1.5 x109/L).
• Hemoglobin of at least 10 g/dL (100 g/L).
• Platelet count of at least 100,000/mm3 (100 x 109/L).
• Total bilirubin within normal limits (benign hereditary hyperbilirubinemias, e.g.Gilbert's syndrome, are permitted).
• Serum alanine aminotransferase, aspartate aminotransferase, and creatinine < 1.5xtimes the upper limit of normal (ULN).
• Life expectancy of at least 6 months based on Investigator's judgment.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
• At least 4 weeks after surgery or radiotherapy before randomization.
• A minimum of 28 days beyond initiation of bisphosphonate or denosumab therapy beforerandomization.
• Recovery from primary local surgical treatment, radiotherapy or orchiectomy beforerandomization.
• Signed informed consent including patient's ability to comprehend its contents.

Exclusion criteria:

• Confirmed brain and/or leptomeningeal metastases (other visceral metastases areacceptable).
• Current symptomatic spinal cord compression requiring surgery or radiation therapy.
• Prior chemotherapy for prostate cancer.
• Patient co-morbidities:
• Subjects who are not indicated for chemotherapy treatment with first lineStandard of Care chemotherapy (docetaxel and prednisone).
• HIV positive, human T-lymphotropic virus positive.
• Active hepatitis B (active hepatitis B), active hepatitis C (HCV), activesyphilis.
• Evidence of active bacterial, viral or fungal infection requiring systemictreatment.
• Clinically significant cardiovascular disease including:
• symptomatic congestive heart failure.
• unstable angina pectoris.
• serious cardiac arrhythmia requiring medication.
• uncontrolled hypertension.
• myocardial infarction or ventricular arrhythmia or stroke within a 6 monthsbefore screening, known left ventricular ejection fraction (LVEF) < 40% orserious cardiac conduction system disorders, if a pacemaker is not present.
• Pleural and pericardial effusion of any NCI CTCAE grade.
• Peripheral neuropathy having a NCI CTCAE ≥ grade 2.
• History of malignant disease (with the exception of non-melanoma skin tumors) inthe preceding five years.
• Active autoimmune disease requiring treatment.
• History of severe forms of primary immune deficiencies.
• History of anaphylaxis or other serious reaction following vaccination.
• Known hypersensitivity to any constituent of the DCVAC/PCa or placebo product.
• Uncontrolled co-morbidities including, psychiatric or social conditions which, inthe Investigator's opinion, would prevent participation in the trial.
• Systemic corticosteroids at doses greater than 40 mg hydrocortisone daily orequivalent for any reason other than treatment of PCa within 6 months beforerandomization.
• Ongoing systemic immunosuppressive therapy for any reason.
• Treatment with anti-androgens, inhibitors of adrenal-produced androgens or otherhormonal tumor-focused treatment performed on the day of randomization (except forGnRH/LHRH agonists or antagonists) to exclude possible anti-androgen withdrawalresponse. This criterion is not applicable to subjects who have never responded toanti-androgen treatment, as there is no risk of anti-androgen withdrawal response.
• Treatment with immunotherapy against PCa within 6 months before randomization.
• Treatment with radiopharmaceutical within 8 weeks before randomization.
• Participation in a clinical trial using non-immunological experimental therapy within 4 weeks before randomization.
• Participation in a clinical trial using immunological experimental therapy (e.g.,monoclonal antibodies, cytokines or active cellular immunotherapies) within 6 monthsbefore randomization.
• Refusal to sign the informed consent.