A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer
A promising immunotherapeutic approach in prostate cancer is whole-cell vaccination.
Irradiated allogeneic tumor cells expressing GM-CSF generate a long-lasting and specific
anti-tumor immunity in preclinical models. Results from several phase I and II trials showed
Prostate GVAX (GVAX) to be well tolerated and suggested improved survival. Cytotoxic
T-lymphocyte-associated antigen 4 (CTLA-4) is a crucial immune checkpoint molecule that
down-regulates T-cell activation and proliferation. Ipilimumab, a fully human monoclonal
antibody (IgG1) that blocks CTLA-4, promotes antitumor immunity, and has been demonstrated
in two phase III trials to improve overall survival in metastatic melanoma patients.
Pre-clinical studies of the anti-CTLA-4 antibody in combination with GM-CSF secreting tumor
cell vaccines demonstrated a potent synergy. In this phase I study the investigators examine
in CRPC patients whether ipilimumab can be safely combined with GVAX. In addition, the
investigators will treat an additional 16 patients at a dose level of 3•0 mg/kg to determine
the safety profile and antitumor effects of GVAX and ipilimumab in patients with CRPC.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of patients with adverse events
Winald Gerritsen, Prof. MD PhD
VU University Medical Center
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)