TENDU Vaccine in Patients With Relapse After Primary Radical Prostatectomy

This is a phase I, dose selection study of safety and effect of different doses of TENDU vaccine, a therapeutic peptide conjugate vaccine, in patients with relapse after primary radical prostatectomy.

This is a open label dose selection study to investigate the safety, tolerability, immune response and preliminary clinical effect of different doses of the TENDU vaccine. TENDU is a synthetic therapeutic peptide conjugate vaccine intended for treatment of prostate cancer.

The patients enrolled in this study is adults with documented progressive disease after radical prostatectomy and who are eligible for salvage radiotherapy and short-term (6 months) androgen deprivation therapy.

All patients taking part at the study must be vaccinated with a Boostrix vaccine (including tetanus antigen) one week prior to the first TENDU vaccine treatment.

Three different doses, 40, 400 and 960 μg of the TENDU vaccine are to be investigated.

The vaccine is administrated by subcutaneous injections with one injection per drug substance (four separate injections) consecutively. The TENDU vaccine will be given four times during a treatment period lasting for 6 weeks and followed up for 6 months after the last treatment.

In total between 12 to 18 patients will be enrolled with a 3+3 design in each dose cohort. The first patient will receive the lowest dose of the TENDU vaccine, and after the treatment is completed, a safety evaluation will be done to evaluate enrolment of the next patients in this cohort. If one patient develops a dose limiting toxicity at a specific dose, an additional three patients are to be enrolled into that same dose cohort, and on the recommended dose an addition of 3 patients will be enrolled.

Eligibility Criteria:
Inclusion Criteria:

1. Males ≥18 years of age
2. PSA rise \>0.2 ng/mL less than 18 months following radical prostatectomy (RP) and pathological ISUP Grade 4-5 (Gleason score \>7), or persisting PSA \>0.1 ng/mL six weeks after RP and short PSA-DT, eligible for salvage radiotherapy and short term androgen deprivation therapy
3. ECOG performance status 0 or 1
4. Adequate organ function as indicated by the following laboratory values:

   * White blood cell count ≥ 2,500/μL
   * Absolute neutrophil count ≥ 1,000/μL
   * Platelets ≥ 100,000/μL
   * Haemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
   * Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
   * Serum total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN
   * AST and ALT ≤ 2.5 x ULN
5. Patients with potential to father children must use an acceptable contraceptive method
6. Written informed consent prior to any study-specific evaluations

Exclusion Criteria:

1. History of hematologic or primary solid tumor malignancy other than prostate cancer with remission less than 3 years prior study enrolment.
2. Metastatic disease assessed by PSMA PET/CT
3. Hypersensitivity to the active substance or any of its excipients
4. Current use of androgen deprivation therapy or radiotherapy to the pelvis
5. Known history or any evidence of active, non-infectious pneumonitis
6. History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting study treatment
7. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
8. Active infection requiring systemic therapy
9. Diagnosis of immunodeficiency
10. Any use of immunosuppressive (cytotoxic chemotherapy, systemic steroids) or immunomodulating agents within 8 weeks of study entry.
11. Hepatitis B or Hepatitis C or Human Immunodeficiency Virus positive
12. Expected to require any other form of systemic or localized antineoplastic therapy during the study
13. Received any other investigational therapy within 4 weeks of the first dose of study treatment
14. Any medical, psychological, social or neurological condition that would make it difficult for the patient to participate in the study and comply with the study procedures, restrictions, and requirements