46IN - Immunotherapy for Advanced Prostate Cancer

Abstract

ABSTRACT While the concept of immunotherapy for cancer has been proposed for many years, proof of principle did not exist. In the context of prostate cancer, the allogeneic cell based agent, GVAX has been tested. GVAX consists of a platform of irradiated hormone sensitive (LNCaP) and hormone resistant (PC-3) prostate cancer cell lines transduced with a replication-defective retrovirus bearing GM-CSF. Unfortunately, two phase III studies in men with metastatic castration resistant prostate cancer (CRPC) failed to demonstrate a survival advantage. More recently, the improved survival observed with sipuleucel-T, an autologous antigen presenting cell (APC)-based agent, for the treatment of patients with metastatic CRPC supports immunotherapy as a valid approach for this disease. Sipuleucel-T uses a fusion antigen of prostatic acid phosphatase and GM-CSF. Evidence exists to support activation of APCs and T cells in an antigen specific fashion and that the degree of activation correlates with overall survival. PROSTVAC-VF TRICOM, a poxvirus vector based PSA antigen targeted vaccine showed promising results in a randomized Phase II study and is now being tested in a international Phase III study. The CTLA-4 inhibiting human monoclonal antibody, ipilimumab, has extended survival in advanced melanoma. Early phase I clinical trials of ipilimumab have yielded clinical and PSA responses in advanced CRPC. A Phase I/II trial was conducted using ipilimumab 10 mg/kg every 3 weeks x 4 with or without prior priming by single fraction of radiation to a metastatic bony site. Results were promising enough to launch 2 phase III clinical trials in men with metastatic CRPC who were either chemo-naive or following prior chemotherapy. The outcomes of these 2 studies are pending. Disclosure P.W. Kantoff: Amgen USA consultant (con), Bayer con, Bellicum con, BIND Biosciences SAB, BN Immunotherapeutics con, Celgene DSMB, Dendreon con, Genetech con, Progenics Pharmaceuticals con, Janssen con, Takeda/Millenium DSMB, Oncogenex DSMB, Tokai con