Chemoablation of metastatic melanoma with rose bengal (PV-10).

Abstract

8534 Background: Intralesional rose bengal (PV-10, 10% RB in saline) can elicit selective chemoablation of solid tumors and an apparent bystander response in untreated lesions. In phase I (20 subjects with AJCC stage III-IV melanoma), a single injection into a total of 114 lesions was well tolerated, yielding durable objective response (OR) at 12-24 weeks in 40% of subjects (20% CR + 20% PR by modified RECIST) and locoregional disease control (CR + PR + SD) in 75% of subjects; 15% of subjects achieved an OR in their bystander lesions (43 lesions). Methods: Phase II testing (80 subjects with measurable Stage III-IV melanoma) commenced at 7 centers in Australia and the USA in October 2007 with enrollment completed in May 2009. After initial treatment of 1-20 cutaneous, subcutaneous or nodal lesions, new or incompletely responsive lesions could be retreated at weeks 8, 12 or 16, with follow-up to 52 weeks. Another 1-2 lesions, including visceral lesions, could remain untreated for assessment of bystander response. The primary end-point is OR of injected target lesions; secondary endpoints include OR of bystander lesions, PFS of target lesions, and plasma PK assessment. Results: The first 40 subjects (median age 75, range 37-92) have completed the study, receiving PV-10 into 486 lesions (mean 1.9 treatment sessions per subject). Adverse events were predominantly mild to moderate, locoregional and transient, the most common being pain at the treatment site (82% of subjects), vesicles or edema (50% each) followed by swelling, pruritus, skin discoloration or headache (18% each), with no grade 4 or 5 AEs attributed to PV-10. Among all 40 subjects, 33% achieved CR, 28% PR and 18% SD of their target lesions; 33% of 21 subjects with evaluable bystander lesions achieved CR in these lesions, along with 10% PR and 14% SD. Mean PFS was 8.5 months (all subjects), while the OR cohort had significantly longer PFS (11.1 months) than SD or PD subjects (2.8 and 2.7 months, respectively). Plasma clearance was bi-exponential (t½ ca. 15 and 120 hrs) consistent with rapid uptake of extravasate and prolonged intralesional retention. Conclusions: Overall, the safety and efficacy profile of PV-10 compares favorably with available and emerging options for this patient population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Provectus Pharmaceuticals Provectus Pharmaceuticals Provectus Pharmaceuticals