Data from the pivotal Phase 3 IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) study, a 512-patient, multi-center, randomized, double-blind, placebo-controlled study evaluating men with asymptomatic or minimally symptomatic, metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC) with overall survival as the primary endpoint, demonstrates that sipuleucel-T (Provenge?, Dendreon Corporation) does extends overall survival in men with CRPC. The data will be presented at the American Society of Clinical Oncology 2010 Genitourinary Cancers Symposium (ASCO-GU) in San Francisco on Friday, March 5 at 1:45 pm PT.
Active Cellular Immunotherapies
Sipuleucel-T is an investigational product candidate for men with advanced prostate cancer and may represent the first in a new class of Active Cellular Immunotherapies (ACIs) specifically designed to engage the patient’s own immune system against cancer. The drug candidate and other ACIs are uniquely designed to use live human cells to engage the patient’s own immune system with the goal of eliciting a specific long-lasting response against cancer. In contrast to Passive Cellular Immunotherapy, where effector cells are infused into the patient but not induced or expanded within the patient, ACI involves inducing an effective response to tumor cells within patients whose immune systems have failed to do so on their own. These methods generally involve introducing tumor antigens to the host effector cells.
A sensitivity analysis performed with longer-term follow-up (36.5 months) and additional events (349 deaths) collected at the time of study closure demonstrated that sipuleucel-T increased three-year survival by 40 percent compared to placebo (32.1% vs 23.0%), the median survival difference of sipuleucel-T compared to placebo was maintained at 4.1 months, with a 24.1% reduction in the risk of death [HR=0.759] and a p-value of 0.017.
As previously reported in a primary analysis (34.1 months median follow-up; 331 deaths), the IMPACT study met its pre-specified primary endpoint of significantly improving overall survival compared to placebo, demonstrating that sipuleucel-T increased three-year survival by 38 percent compared to placebo (31.7% vs 23.0%), extending median survival by 4.1 months compared to placebo (25.8 months vs. 21.7 months), with a 22.5 percent reduction in the risk of death [HR=0.775] and a p-value of 0.032.
In addition, new analyses demonstrated that the median predicted survival of the two treatment arms using the Halabi model were well balanced (20.3 months for sipuleucel-T vs 21.2 months for placebo). Furthermore, in an analysis in which patients were censored at the time of docetaxel use, the sipuleucel-T treatment effect remained strong [HR=0.649].
As previously reported, the most common adverse reactions were chills, fever, headache, aches, influenza-like illness and sweating.
“The results from the IMPACT study corroborate earlier studies with sipuleucel-T in demonstrating an improvement in overall survival for men with metastatic castration resistant prostate cancer. This is the first therapeutic vaccine to demonstrate a survival benefit in cancer,” said Philip Kantoff, M.D., Director of the Lank Center for Genitourinary Oncology, Chief of the Division of Solid Tumor Oncology, and Chief Clinical Research Officer at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School, and principal investigator of the IMPACT study. “Furthermore, the results of this study validate cancer immunotherapy as an entirely new treatment paradigm that can provide patients with a clinically meaningful survival benefit coupled with a well-tolerated safety profile.”
Dendreon Corporation is seeking licensure for sipuleucel-T for men with metastatic CRPC and submitted an amended Biologics License Application for which the U.S. Food and Drug Administration assigned a Prescription Drug User Fee Act date of May 1, 2010.