Data on PV-10 combination therapy presented at AACR Annual Meeting

Provectus Pharmaceuticals, Inc.Apr 11 2013

Provectus Pharmaceuticals, Inc. (OTCQB: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, presented data on PV-10 combination therapy today at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.

“Combination of PV-10 Immuno-chemoablation and Systemic Anti-CTLA-4 Antibody Therapy in Murine Models of Melanoma”

The presentation, based upon Abstract #4755 entitled, "Combination of PV-10 Immuno-chemoablation and Systemic Anti-CTLA-4 Antibody Therapy in Murine Models of Melanoma," was authored by Eric Wachter, Savannah Blair, Jamie Singer and Craig Dees, all of Provectus Pharmaceuticals. The poster was presented by Dr. Wachter, Chief Technology Officer.

PV-10 is Provectus Pharmaceuticals's novel oncology drug designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects. Previous preclinical and clinical studies have established that upon intralesional (IL) administration, PV-10 localizes to injected tumor tissues while rapidly clearing from healthy tissue. Intralesional injection with PV-10 focuses the ablative impact on injected tumors and minimizes the potential for systemic side effects, making it an attractive candidate for both monotherapy and for combination therapy with other agents.

In Phase 2 testing PV-10 elicited an objective response rate of 51% in melanoma patients (CR: 25%; PR: 26%) after 1-4 treatment cycles, with a third of patients experiencing an objective response in their monitored untreated tumors (CR: 26%; PR: 7% in 42 patients with monitored untreated lesions). This apparent immune-mediated bystander response was highly correlated with successful ablation of injected tumors. Recent mechanism studies in B16 murine melanoma tumor lines have confirmed that PV-10 ablation induces T-cell mediated tumor-specific immunity, resulting in marked suppression of untreated metastases and tumor-specific IFN-ˠ production.

The data presented today at AACR utilized systemic immune stimulation by the anti-CTLA-4 antibody 9H10 to explore the potential benefit of combination therapy with PV-10 immuno-chemoablation in murine melanoma. Because advanced melanoma patients, particularly those with stage IV disease, have substantial tumor burden in areas that are often non-accessible to injection with PV-10, combination of PV-10 with systemic therapy may afford advantage in control of uninjected disease while the immunologic effects of PV-10 reach full potential. By combining PV-10 with the anti-CTLA-4 antibody 9H10 in very aggressive murine models of metastatic disease, researchers at Provectus aimed to ensure that any systemic treatment was potentially safe in combination with PV-10, and that efficacy signals from the combination therapy could be differentiated from those of PV-10 alone.

In order to discriminate the systemic effect of PV-10 alone from that in combination with CTLA-4 blockade, 3 dose levels of 9H10 were assessed in bilateral B16-F10 melanoma flank tumor models, using four treatment groups at each level randomized by tumor burden immediately prior to commencement of treatment. In this model, once palpable tumors were present in both flanks, one flank tumor was injected with PV-10 or saline control, with 9H10 or saline control administered systemically to complete the combination regimen. PV-10 and PV-10 plus 9H10 exhibited robust response in both treated and untreated tumors. The combination therapy was most effective in the low dose model, where advantages in tumor growth and survival benefit were most pronounced. Increased apparent toxicity of 9H10 at the higher dose levels highlighted the need for establishment of an optimal dose in future mechanism studies and clinical trials.

Dr. Eric Wachter commented, "Results of these studies demonstrate that immuno-chemoablation with PV-10 is highly effective when all tumors are accessible for injection, providing rapid reduction of tumor burden and tumor-specific immunity. PV-10's rapid tumor ablation and immunologic stimulation, combined with its distinctive adverse effects profile and pharmacology that minimizes the potential for drug interaction, represent a unique and powerful approach that could complement many systemic cancer therapies. This work shows that, as hypothesized, addition of the immunologic effects of an anti-CTLA-4 agent augments the benefits of PV-10. For visceral or other inaccessible disease, combination of PV-10 with CTLA-4 blockade offers important potential for synergy."

Dr. Wachter continued, "PV-10 is currently entering pivotal Phase 3 testing as a monotherapy for locoregional control of cutaneous metastatic melanoma. These data on the potential benefits of combination therapy are encouraging, particularly for advanced melanoma patients with substantial tumor burden inaccessible to PV-10 injection. PV-10's ability to reduce tumor burden and elicit tumor-specific immunologic stimulation make it a logical potential complement to anti-CTLA-4 agents, such as ipilimumab. We believe these results warrant a Phase 1/2 dose escalation trial with 'ipi' to validate this effect and potentially advance the options available to patients."