141599-159

Combining active immunotherapy and immune checkpoint inhibitors in prostate cancer.

Category: 
Genitourinary Cancer
Session Type and Session Title: 
General Poster Session A: Prostate Cancer
Abstract Number: 

172

Poster Board Number: 
General Poster Session A (Board #H8)
Citation: 
J Clin Oncol 33, 2015 (suppl 7; abstr 172)
Author(s): 
Harpreet Singh, Ravi Amrit Madan, William L. Dahut, Geraldine Helen O'Sullivan Coyne, Myrna Rauckhorst, Sheri McMahon, Christopher Ryan Heery, Jeffrey Schlom, James L. Gulley; Genitourinary Malignancies Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Medical Oncology Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Laboratory of Tumor Immunology and Biology, National Cancer Institute at the National Institutes of Health, Bethesda, MD

Abstract Disclosures

Abstract: 

Background: Results of recent clinical trials have intensified interest in immunotherapy in oncology. A number of cancer immunotherapies have been approved recently, while others are in late stage clinical development. The poxvirus-based active immunotherapy, PROSTVAC is generally well tolerated and is currently being evaluated in a global Phase 3 randomized, placebo-controlled trial. Ipilimumab, an approved immune checkpoint inhibitor in melanoma, is also being evaluated in a Phase 3 trial in chemo-naïve mCRPC. Methods: Results of two Phase 2 trials in men with mCRPC who were treated with PROSTVAC alone were compared with results from a Phase 1 combination study in mCRPC patients treated with PROSTVAC plus escalating doses of ipilimumab. Patients were enrolled in the Phase 1 combination study when docetaxel was the only FDA-approved mCRPC treatment that improved overall survival (OS). Results: In a multicenter Phase 2 trial, 125 men were randomized 2:1 to receive PROSTVAC or placebo. Patients treated with PROSTVAC had improved OS compared to placebo (25.1 vs 16.6 months; HR 0.56; 95% CI 0.37-0.85).Similar data was seen in a second phase 2 trial of PROSTVAC, where 32 patients with mCRPC had a median OS of 26.6 months (predicted median OS by the Halabi nomogram was 17.4 months). In a Phase 1 combination study of 30 mCRPC patients with similar baseline characteristics (predicted median OS of 18.5 months), patients were treated with PROSTVAC plus escalating doses of ipilimumab. The observed median OS was 31.3 months for all dose cohorts and 37.2 months for patients treated at 10 mg/kg based on updated overall survival data. Furthermore, there appears to be a tail on the curve with approximately 20% of patients at 10 mg/kg alive at 80 months. Conclusions: The comparison of data from three independent trials of PROSTVAC active immunotherapy in three similar patient populations provides hypothesis-generating data that the addition of an immune checkpoint inhibitor may have a positive effect on overall survival through a potential synergy in mechanism of action. The updated long term survival data is further evidence of improved OS with PROSTVAC. Future randomized trials are being planned to prospectively evaluate this hypothesis. Clinical trial information: NCT00113984