by ecancer reporter Janet Fricker

Injecting cutaneous melanoma sites of stage III-IV patients with PV-10 (Rose Bengal) delivered sustained high response rates, reports an open label phase 2 study.

The study, presented at the European Society for Medical Oncology meeting in Vienna, Austria, revealed an additional ‘bystander’ effect in nearby non injected lesions.

Rose Bengal is a derivative of fluorescein, an agent that has been used for over 80 years to stain necrotic tissue in the cornea and as an IV diagnostic of liver impairment.

Its novel use in melanoma was discovered by Provectus Pharmaceuticals Inc (Knoxville, Tennessee, USA) while exploring different formulations for use in photodynamic cancer therapy.

By serendipity the company discovered that PV-10, a formulation developed to be administered directly into solid tumours, destroyed tumours without the need for light activation.

“PV-10 appears to be selectively toxic to cancer cells via chemoablation, and also to produce a bystander effect where it elicits an immune response causing spontaneous regression of nearby melanoma tumours that haven’t been injected,” explained the study presenter, Dr Sanjiv Agarwala, from St Luke’s Hospital and Health Network in Bethlehem, Pennsylvania, USA. The approach, he added, was only applicable to a subset of melanoma patients with cutaneous accessible disease.

In the phase 2 open label single arm trial, 80 patients with stage III-IV melanoma received up to four courses of PV-10 injected in up to 20 cutaneous or subcutaneous lesions on the extremities and, or torso. For each, a bystander lesion was identified that underwent biopsy to confirm melanoma, but did not undergo injection. Patients were treated at seven centres in Australia and the USA.

Results showed that an objective response rate (OR) was achieved in 51% of subjects’ targets lesions (25% complete response and 26% partial response). Furthermore, disease control (combined Complete, Partial and Stable Response) was achieved in 69% of lesions.

When bystander lesions were monitored, 33 % of subjects received an OR in their bystander lesions, while 50% achieved disease control in these lesions.

Overall survival (OS) data showed Stage III subjects achieved a mean overall survival of at least 12.6 months (median not reached during the study interval) versus 7.3 months for Stage IV subjects. The most common side effects were injection site pain, oedema and injection site vesicles.

“These results further confirm the robust response that can be achieved with PV-10 that was first seen in a preliminary report presented in 2010 in 20 patients. The study showed that the patients who respond do better and live longer,” said Dr Agarwala.

The abstract also included MRI scans of two patients in the study treated with PV-10 showing regression of lung metastasis. “These were small lesions. It was an interesting observation but we will need a randomized study to demonstrate the effect,” said Dr Agarwala.

The company provided further guidance on the final design for its proposed Phase 3 randomized control trial which would involve approximately 180 subjects with Stage III-IIIC melanoma, who would be randomized to PV-10 or systemic chemotherapy. The trial, which will have  progression free survival as the primary endpoint, is expected to start in early 2013 at centres in Australia, the US and EU.

In future, added Dr Agarwala, PV-10 was likely to be used in combination with other agents, such as ipilimumab and vemurafenib, with a need to develop treatment algorithms to explore how the different approaches will fit together. “Additionally, injection with PV-10 could be used as an adjuvant treatment to trigger an immune response prior to surgical removal of the tumours,” he said.

Reference

S Agarwala, J Thompson, B Smithers, et al. “Immuno-chemoablation of metastatic melanoma with intralesional rose Bengal.” Abstract 1137P.