Novel Rose Bengal Formulation Obliterates Lesions in Patients with Deadliest of Melanomas

Source: Newswise, Spetember 2014

Data Presented at the European Society for Medical Oncology Congress in Spain Shows New Approach offers Overall Response Rate of 71%

A formulation of the dye, rose bengal, which has been around for more than a century, has recently been shown to have promise in patients with cutaneous melanoma, one of the deadliest forms of the disease. Originally used as a coal tar–derived wool dye, rose bengal has most commonly been used as a stain for detecting ocular conditions starting in the 1930s.

This mild-mannered stain, however, turns into a cancer killing superhero when properly prepared and injected into melanoma lesions. Furthermore, the drug has been shown to create what experts call mediated tumor-specific immune response to cancer. Completed Phase II data was recently presented at the European Society for Medical Oncology 2014 Congress in Madrid that detailed the safety and efficacy of intralesional (IL) treatment of refractory cutaneous melanoma with rose bengal disodium. The data came from an 80 patient international, multicenter, single arm phase II trial.

Sanjiv S. Agarwala, MD, an internationally recognized investigator in the field of melanoma and immunotherapy and chief of medical oncology and hematology for St. Luke’s University Hospital & Health Network, based in Bethlehem, Pa, titled his abstract “Subgroup Efficacy in Patients Receiving Intralesional Rose Bengal to All Existing Melanoma in Phase II Study PV-10-MM-02.”

Dr. Agarwala found patients refractory to a median of 6 previous interventions with 6.3cm median sum lesion diameter in biopsy-confirmed melanoma received PV-10 – the 10% rose bengal solution currently produced and being investigated by Provectus Biopharmaceuticals. Dr. Agarwala has published a variety of therapeutic approaches to melanoma and has led promising clinical trials in immunotherapy and targeted therapy of melanoma. He co-authored the book “Melanoma: Translational Research and Emerging Therapies” to help bridge the gap between research and clinical approaches to melanoma therapy.

Dr. Agarwala detailed in his presentation of the secondary effects of PV-10 to the cancerous lesions. “Although the primary ablative effect is responsible for complete response in injected lesions, durability of response and bystander response observed in this study implicate an immunologic mechanism of action secondary to ablation,” states Dr. Agarwala. Dr. Agarwala’s team started by injected the rose bengal solution into as many as 20 cutaneous and subcutaneous lesions up to 4 times over a 16-week period with patients followed for 52 weeks. The team found that they achieved the best overall response rate (BORR) assessed in up to 10 injected target lesions.

Overall, the team at St. Luke’s found that PV-10 was well tolerated and 41 of 80 patients met the primary endpoint of objective response (Complete Response + Partial Response) in their injected target lesions (51% ORR CI 40-63%, 26% CR). In the subgroup of 28 patients who received PV-10 into all existing melanoma lesions, ORR was 71% (CI 51-87%) with 50% CR (CI 31-69%). In these patients plus 26 other patients with uninjected disease limited to bystanders (i.e., 54 patients in all) CR was achieved in 232 of 363 injected lesions (64% CR): 121 lesions required a single injection for CR, 84 required 2 injections, 22 required 3 injections and 5 required 4 injections. Additionally, 10 of 28 uninjected bystander lesions achieved complete response.

Eric Wachter, PhD and Chief Technology Officer of Provectus, said, “We are very pleased to share the patient-level PFS data at ESMO that defined our design parameters for the upcoming phase 3 trial. These study results demonstrate the potential of an intralesional approach to delay progression while alleviating symptoms of locally advanced melanoma.”

Wachter continued, “We are looking forward to initiation of the phase 3 trial and have assembled an experienced multi-disciplinary team to help us execute this important study. For example, we are thrilled to collaborate with ERT, Inc., experts in quantifying patient reported outcomes for pivotal oncology trials, and expect this collaboration to help place Provectus at the forefront in the study of cutaneous symptoms of locally advanced melanoma.”

Wachter concluded, “The data presented at ESMO were fundamental in allowing us be in a position to commence pivotal testing of PV-10 in locally advanced melanoma patients. Furthermore, understanding the bystander effect is critical to rational combination of PV-10 with systemic drugs in patients with significant disease inaccessible to intralesional injection, and we look forward to seeing additional data on this important topic in coming months.”

The abstract can be accessed via the following link: http://www.pvct.com/publications/Provectus-ESMO-2014-09-28.pdf

 

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