Background: PV-10 (10% rose bengal disodium) is a small molecule immuno-chemoablative agent that has completed phase 2 testing in 80 AJCC Stage IIIB-IV(M1c) subjects in clinical trial PV-10-MM-02 (ClinicalTrials.gov ID NCT00521053, sponsored by Provectus Pharmaceuticals, Inc.). Upon intralesional injection, PV-10 elicits selective ablation of injected lesions and a tumor-specific, immune-mediated bystander response in untreated lesions in which T cells are implicated.
Materials and Methods: In the phase 2 trial, up to 10 cutaneous or subcutaneous target lesions and up to 10 additional non-target lesions received intralesional PV-10 at day 0 and could be reinjected as necessary at weeks 8, 12 and 16 if tumor tissue remained. Up to 2 additional cutaneous or subcutaneous lesions were left untreated to assess bystander response. The primary endpoint in the single arm trial was best overall objective response rate (BORR) judged by RECIST in each subject's target lesions.
Results: For all subjects, BORR was 51% (26% CR, 25% PR) with the amount of tumor burden accessible to PV-10 injection prognostic for outcome. In the majority of subjects (66%) the lesions treated with PV-10, together with up to 2 untreated bystander lesions, constituted all disease present, and these subjects achieved a BORR of 62%, while when all disease was treated (33% of subjects) BORR further increased to 73%. Locoregional blistering was observed in 40% of subjects, occurring within 7 days of PV-10 injection but with no clear pattern of incidence, and generally resolving without sequelae within 4 weeks. Occurrence of this potentially immune mediated phenomenon was strongly prognostic for outcome, with 66% BORR in subjects with blisters vs. 42% in those not developing blisters. Locoregional disease control correlated stronger still: 90% of subjects with blisters achieved stable disease or better vs. 54% of subjects without blisters.
Conclusions: In this patient population refractive to other local treatments such as surgery and radiation, intralesional PV-10 provided a viable strategy to maintain, with minimal intervention, locoregional control of the disease with the potential to delay, reverse or prevent progression to life-threatening visceral disease.
Conflict of interest: Ownership: Provectus Pharmaceuticals (Singer, Wachter). Advisory board: Provectus Pharmaceuticals (Agarwala, Thompson, Ross, Scoggins). Corporate-sponsored research: Provectus Pharmaceuticals (Agarwala, Thompson, Smithers, Ross, Coventry, Minor, Scoggins). Other substantive relationships: Employee, Provectus Pharmaceuticals (Singer, Wachter)