A Phase II Randomised Trial of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer

GX301, an experimental therapeutic (anti-cancer) vaccine, is composed of four immunogenic peptides from human telomerase and two complementary adjuvants, Montanide ISA-51 VG and imiquimod.

An earlier Phase 1 study of GX301 has provided evidence of vaccine-specific immune response in a small sample of stage 4 prostate cancer patients given eight GX301 administrations over 9 weeks.

The present Phase 2, randomised, parallel-group, multicentre trial is aimed at comparing three different GX301 administration regimens in patients with progressive, castration-resistant prostate cancer who have completed a first-line docetaxel treatment and have achieved response to chemotherapy or disease stability. Primary comparisons will include regimen efficacy in inducing vaccine-specific immunological responses over a period of 6 months following randomisation; and treatment safety and tolerability over the same period.

A further study aim is to investigate whether achievement of immunological response, irrespective of the assigned GX301 regimen, is related to progression-free and/or overall survival.

Eligible patients will be randomly assigned to receive one of three GX301 vaccination regimens consisting of two, four or eight administrations, respectively, each regimen being given over a fixed 9-week period. Randomisation ratio will be 1:1:1. Randomisation will be stratified by previous cumulative exposure to docetaxel.

Following randomisation, immunological responses to GX301 will be determined over a 6-month period. However, on-study patient observation will be continued until the occurrence of one of the following end-points, whichever the earliest: (a) disease progression; (b) death; (c) completion of an 18-month observation period; or (d) patient's decision to terminate his participation in the study.

All patients discharged from the trial for reasons (a) or (c) will undergo a follow-up to ascertain survival until 24 months from randomisation.

Data analysis will be carried out in two sequential steps. The first step will focus on co-primary outcomes and will therefore take place upon completion of the study dataset up to the 6-month time-point. The second step will incorporate secondary outcomes and will therefore be conducted upon completion of the full study dataset.

Inclusion criteria

Documented patient history

• Histologically confirmed diagnosis of prostate cancer, with an available Gleason score.
• Diagnosis of progressive, castration-resistant prostate cancer (CRPC), leading to inception of first-line chemotherapy with a docetaxel-based regimen.
• Completion of chemotherapy with a cumulative delivered dose of 300 to 825 mg/m2 docetaxel.

Note: Pre-chemotherapy exposure to abiraterone and prednisone does not preclude eligibility, provided that both agents have been discontinued prior to initiation of docetaxel.

Current patient status

• Ability to understand study-related patient information and provision of written informed consent for participation in the study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 6 months.
• An interval ≥4 weeks elapsed from the last docetaxel administration.
• Documented achievement of response or disease stability with docetaxel chemotherapy.
• Absence of cancer-related symptoms suggesting clinical disease progression.
• Current castrate testosterone level (≤50 ng/dL) due to current gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy or past orchiectomy.
• Haematology and blood chemistry tests within specified limits.
• Successful recovery from acute toxicities from prior chemotherapy.
• Confirmation from the immunology laboratory that the blood sample provided for baseline immunological tests is technically adequate.

Exclusion criteria

• Known intolerance to Montanide or imiquimod.
• Known presence of brain metastatic disease or spinal cord compression.
• Radiotherapy within the past 4 weeks.
• Concomitant presence of other primary malignancy
• Major surgery within 4 weeks prior to randomisation.
• Cardiovascular illness or complication which, in Investigator's judgment, compromises prognosis at 6 months or prevents the patient from following study procedures.
• Serious uncontrolled infection.
• Known presence of active autoimmune disease.
• Known presence of acquired, hereditary, or congenital immunodeficiency.
• HIV infection.
• Current need for immunosuppressive drug therapy, including systemic corticosteroids.
• Current need for denosumab therapy. (Patients under bisphosphonate treatment are eligible).
• Skin disease interfering with evaluation of local tolerance of GX301 injections.
• Participation in any interventional drug or medical device study within 30 days prior to treatment start.