The VIABLE study sought to confirm the hypothesis that the combination of docetaxel with DCVAC/PCa followed by a maintenance therapy with DCVAC/PCa would improve overall survival in patients with metastatic castration-resistant prostate cancer.

This was a randomized, double blind, placebo-controlled, multicenter, international, parallel-group phase III study. Patients with metastatic castration-resistant prostate cancer who were candidates to receive standard of care first-line chemotherapy with docetaxel plus prednisone were randomized 2:1 into one of two arms: an investigational arm (DCVAC/PCa) and a control arm (placebo) in addition to chemotherapy (docetaxel plus prednisone).

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 the following criteria:

  • Confirmed pathological fracture related to the disease OR
  • Confirmation of distant bone and/or soft-tissue and/or visceral metastases on CT or 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 the minimum PSA as reached during ADT or above the pre-treatment level, if no response was observed and which is confirmed by a second value 1 or more weeks later OR
  • Progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per RECIST v1.1 criteria, confirmation by an independent review facility (IRF) required OR
  • Two or more new lesions appearing on bone scan/imaging compared with a previous scan (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/ luteinizing hormone-releasing hormone (GnRH/LHRH) agonists or antagonists to reach levels of serum testosterone of ≤ 1.7 nmol/L (50 ng/dL). The duration of the castration period must be at least 4 months before screening as evidenced by combination of clinical/laboratory data (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 < 1.5x times 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 before randomization.

• Recovery from primary local surgical treatment, radiotherapy or orchiectomy before randomization.

• Signed informed consent including patient's ability to comprehend its contents.

Exclusion criteria:

• Confirmed brain and/or leptomeningeal metastases (other visceral metastases are acceptable).

• 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 line Standard of Care chemotherapy (docetaxel and prednisone).

  • HIV positive, human T-lymphotropic virus positive.

  • Active hepatitis B (active hepatitis B), active hepatitis C (HCV), active syphilis.

  • Evidence of active bacterial, viral or fungal infection requiring systemic treatment.

  • 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 months before screening, known left ventricular ejection fraction (LVEF) < 40% or serious 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) in the 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, in the Investigator's opinion, would prevent participation in the trial.

• Systemic corticosteroids at doses greater than 40 mg hydrocortisone daily or equivalent for any reason other than treatment of PCa within 6 months before randomization.

• Ongoing systemic immunosuppressive therapy for any reason.

• Treatment with anti-androgens, inhibitors of adrenal-produced androgens or other hormonal tumor-focused treatment performed on the day of randomization (except for GnRH/LHRH agonists or antagonists) to exclude possible anti-androgen withdrawal response. This criterion is not applicable to subjects who have never responded to anti-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 months before randomization.

• Refusal to sign the informed consent.