Abstract 4755: Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of melanoma

Autor: Craig Dees, Savannah Blair, Eric A. Wachter, Jamie Singer
Rok vydání: 2013
Předmět:
Zdroj: Cancer Research. 73:4755-4755
ISSN: 1538-7445
0008-5472
Popis: Rose bengal disodium (PV-10) is an investigational small molecule ablative agent currently entering pivotal phase 3 clinical testing as a monotherapy for locoregional control of cutaneous metastatic melanoma. Upon intralesional (IL) administration, PV-10 localizes to the injected tumor tissues while clearing rapidly from healthy tissue. Tumor infiltration with PV-10 leads to rapid necrosis of the injected lesion, with complete resolution common within 2-8 weeks. In phase 2 testing in 80 patients with Stage IIIB-IV(M1c) melanoma, IL PV-10 elicited an objective response in injected tumors in 51% of patients (CR:25%, PR:26%) after 1-4 treatment cycles. In addition to this direct ablative effect on injected tumors, some patients achieved an objective response in their monitored untreated tumors (CR:26%, PR:7% in 42 subjects with monitored untreated lesions) in an apparent immune-mediated bystander response that highly correlated with successful ablation of their injected tumors. Treatment was generally well tolerated, with adverse events confined mainly to the injection site and no grade 4 or 5 adverse events associated with use of PV-10. Recent nonclinical testing in the B16-F10 murine melanoma tumor line has confirmed that PV-10 ablation induces tumor-specific immunity, resulting in marked suppression of synchronous lung metastases upon ablation of a flank tumor and tumor-specific IFN-γ production. In this study we assess potential benefit of combination of PV-10 immuno-chemoablation with the hamster anti-murine CTLA-4 antibody 9H10 in bilateral flank and lung metastasis models (B16-F10 melanoma in C57BL/6 mice). Results from these models will be reported and could support clinical development of combination therapy in advanced melanoma patients, such as stage IV patients with substantial tumor burden in locations inaccessible to PV-10 injection. The rapid reduction in tumor burden and tumor specific immunologic stimulation provided by PV-10 may complement the immune stimulation of anti-CTLA-4 antibodies such as ipilimumab without increased toxicity. Citation Format: Eric A. Wachter, Savannah Blair, Jamie Singer, Craig Dees. Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4755. doi:10.1158/1538-7445.AM2013-4755
Databáze: OpenAIRE
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