DCVax® - Prostate: Phase III
Development stage: DCVax®-Prostate is entering a Phase III clinical trial that was cleared to proceed by the Food and Drug Administration in January of 2005. Data from a Phase I/II clinical trial support the overall safety of DCVax®-Prostate, and suggest that DCVax®-Prostate may induce an immune response . Clinical data obtained in this trial also suggest delayed times to progression of disease, especially in patients with no metastatic disease at entry.
Trial design: The Phase III clinical trial is a randomized, multi-center, double blinded clinical trial that will enroll 612 patients in the United States.
Indication: Patients with hormone independent, non-metastatic prostate cancer will be eligible for participation in this clinical trial. Other eligibility criteria include requirements around absolute PSA levels as well as PSA doubling time.
Endpoints: The primary endpoint for the Phase III clinical trial is survival free of disease progression. The first secondary endpoint is survival free of the development of symptoms arising from progression of disease. Other endpoints include the induction of immune responses, and overall survival.
Product: DCVax®-Prostate is manufactured using a patient’s own dendritic cells, loaded with a recombinant form of Prostate Specific Membrane Antigen (rPSMA). The dendritic cells are generated from monocytes obtained through a single leukapheresis.
Immunization schedule: Immunization starts when eligible patients have met all entry criteria, including the specified absolute PSA level and PSA doubling time. Immunizations will be given at weeks 0, 2, 4, 8, and at months 3, 6, 9, 12, 18, 24 and 30.
Previous Phase I/II Clinical Trials
The Phase I/II study evaluated 32 patients with hormone independent prostate cancer, both non-metastatic and metastatic. Twelve patients entered the study with no radiological evidence of metastatic disease, and 20 had between one and three bone and/or lymph node metastases.
The natural history of prostate cancer indicates that patients with rising PSA values while on hormone treatment progress to metastatic disease on average in about 28-36 weeks, dependent upon several prognostic factors such a PSA velocity, time on anti-androgen therapy and nadir PSA while on anti-androgen therapy. In the non-metastatic group of patients (n=12), none had progressed at 28 weeks and only half had progressed at 59 weeks. Based on these Phase I/II data, the delay of progression to metastatic disease during long-term follow-up of this subset of patients appears correlated with stabilization of PSA levels. This is the patient population that the company will focus on in the Phase III clinical trial.
We also measured a highly specific PSMA antibody response following immunization with DCVax®-Prostate, and a highly specific and strong T cell response to PSMA in about 80% of the patients treated with DCVax®-Prostate. Northwest Biotherapeutics’ expectation based on these data is that administration of DCVax®-Prostate will enhance progression free survival relative to placebo, delay the development of symptomatic disease and increase overall survival.
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