Released via Provectus News today: The Meeting Highlights section of the September 2012 edition of Pharmacy and Therapeutics, (Vol. 37, No. 9, pgs. 527-528), covers selected sessions from the 2nd European Post-Chicago Melanoma Meeting 2012, including the session on intralesional PV-10 (reproduced below).
PV-10 is a sterile, non-pyrogenic solution of Rose Bengal disodium (10% RB) for intralesional injection. It has an established safety history in prior diagnostic and ophthalmic use. PV-10 is not metabolized; it has a short circulatory halflife of about 20 minutes. PV-10 is excreted via bile. It accumulates selectively in the lysosomes of cancer cells and elicits autolysis within 30 to 60 minutes.
Dr. Agarwala’s seven-center phase 2 trial in the U.S. and Australia enrolled 80 patients with stage III/IV melanoma. The median age of the patients was 70.0 years, and 61% were men. In this study, which was completed in June 2012, investigators treated up to 10 target lesions and observed one or two untreated bystander lesions. Re-treatment of new or partially responsive lesions was allowed as necessary.
Subjects received from one to four treatments (median, two treatments). The median dose was 1.6 mL, and the median cumulative dose was 3.4 mL. Adverse events were predominantly locoregional and mild to moderate. No grade 4 or 5 events were reported, but there were seven reports of grade 3 injection-site pain.
The objective response rate (defined as complete response + partial response) was 58% in target lesions and 40% in bystander lesions. Locoregional disease control (defined as the addition of stable disease to complete and partial responses) was reported for 80% of the target lesions and for 60% of the bystander lesions. Bystander effects in untreated lesions correlated closely with responses in injected lesions. A systemic response was defined as stasis or regression of distant visceral lesions in several patients.
The new analysis reported by Dr. Agarwala focused on responses of target lesions stratified according to disease stage. Stage III melanoma subjects exhibited consistently robust responses to PV-10. Furthermore, responses were significantly more durable in stage III patients (mean, 9.6+ months) compared with 3.1 months for stage IV melanoma patients (P < 0.001).
Response rates in stage IV patients were adversely affected by greater target tumor burden at baseline and by the progression of non-study lesions that precluded repeated treatment.
Dr. Agarwala noted that the planned phase 3 trial of PV-10 will include about 180 subjects with stage IIIb and IIIc disease.
In an interview, Dr. Sondak noted that locally or regionally advanced tumors without metastatic disease can be a severe problem for patients and for surgeons.
“The logical approach is a localized one,” he said.
However, whereas radiation would be the obvious solution for many cancers, melanoma is notoriously poorly responsive to this treatment. Fortunately, Dr. Sondak said, a number of tools have come along to treat this group of patients; some— like V-TEK (OncovexGM-CSF) and PV-10—create an immune effect.
He said further, “If it’s shown that they are causing local destruction of tumors and are causing T-cell infiltrates, I’m interested in seeing how I can take advantage of that. If phase 3 trials confirm their benefits, adding systemic immunological therapies like ipilimumab and PD-1 with intralesional injection therapies would be an extremely logical combination.”