Provectus Pharmaceuticals, Inc. : Intralesional PV-10 Shows High Response Rate in Advanced Melanoma, Evidence of Systemic Effects: Presented at ECCO-ESMO-ESTRO Congress

By Walter Alexander

AMSTERDAM, Netherlands -- October 3, 2013 -- The immuno-chemoablative agent 10% rose bengal disodium (PV-10) demonstrated favourable response rates in 80 patients with advanced melanoma in an updated analysis of a phase 2 study, presented at the 2013 European Cancer Congress (ECC).

A correlation between blistering and response also was observed, supporting other evidence that PV-10 causes a systemic response, stated lead author Sanjiv S. Agarwala, MD, Temple University, Philadelphia, Pennsylvania, speaking here on September 30.

Among patients in whom all lesions could be injected, 71% of patients had either complete or partial responses. Also in this subgroup, the clinical response rate (complete response plus partial response plus stable disease [locoregional disease control]) was 85%, Dr. Agarwala said.

Participants in this study all had stage IIIB-IV melanoma, and were refractory to a median of 6 prior interventions. All subjects had up to 10 cutaneous or subcutaneous target lesions treated with intralesional PV-10, which were reinjected if necessary at weeks 8, 12, and 16. Up to 2 additional cutaneous or subcutaneous lesions were left untreated to assess "bystander" response. The primary endpoint was best overall response rate in up to 10 target lesions.

"The principle is that this agent has a local chemoablative effect, one where we believe it enters into lysosomes causing local necrosis, and sometimes blistering of the lesion -- and then, in some patients, a systemic effect that we believe is immunologically mediated," Dr. Agarwala explained. Further evidence of systemic effects, he noted, comes from a 54% complete plus partial response rate in uninjected "bystander" lesions.

For all subjects, best overall response was 51% (26% complete, 25% partial). The amount of tumour burden accessible to PV-10 injection was prognostic for outcome, with both magnitude and duration of response inversely related to untreated tumour burden.

For patients in whom all lesions (except for up to 2 untreated "bystander" lesions) could be treated, the best overall response rate was 63%. In subjects where all disease was treated, as noted above, the complete (50%) plus partial (21%) rate further increased to 71%.

In target lesions, the complete plus partial plus stable disease rate was 54% for patients without blistering and 91% among those with blistering (P = .001).

Dr. Agarwala proposed 3 possible scenarios for PV-10 use -- for if and when it receives approval. First, it might be used in patients who are refractory to all other therapies and who have injectable disease. Second, it might be used in patients who have injectable lesions but who are not eligible for systemic therapy (e.g., the elderly or those with comorbidities). Third, it might be used in combination with other therapies (e.g., ipilimumab or nivolumab or both). "Of course, all of these need to be tested in clinical trials," he said.

A further option for PV-10 use, Dr. Agarwala added, would be in an attempt to turn unresectable lesions into resectable ones.

"Beyond this, many of my surgical colleagues are interested in the idea of using PV-10 to stimulate the immune system before surgery to potentially lower the odds of recurrence," he commented.

A phase 3 trial of PV-10 is in the planning stages.

The 2013 European Cancer Congress is the 17th congress of the European CanCer Organisation (ECCO), the 38th congress of the European Society for Medical Oncology (ESMO), and the 32nd congress of European Society for Therapeutic Radiology and Oncology (ESTRO).

[Presentation title: Locoregional Disease Control in Metastatic Melanoma: Exploratory Analysis from Phase 2 Testing of Intralesional Rose Bengal. Abstract 3755]