Provectus Biopharmaceuticals Inc (PVCT)

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Immunotherapy Bridge 2017 and Melanoma Bridge 2017: meeting abstracts


P5 Oncolytic immunotherapy with PV-10
Sanjiv Agarwala, B. Mark Smithers, Axel Haushild, Paolo A. Ascierto, Eric Watcher

1St Luke’s University Hospital and Health Network, Easton, Pennsylvania, USA; 2Princess Alexandra Hospital, Brisbane, Queensland, Australia; 3Department of Dermatology, University Hospital Schleswig–Holstein, Kiel, Germany; 4Istituto Nazionale Tumori IRCCS Fondazione “G Pascale”, Naples, Italy; 5Provectus Biopharmaceuticals, Inc., Knoxville, Tennessee, United States


Journal of Translational Medicine 2018, 16 (Suppl 1):P5


Background: PV-10 is an investigational small molecule oncolytic immunotherapy (10% w/v rose bengal disodium for injection). Intralesional (IL) injection can elicit a primary, local effect in injected tumor tissue (immunogenic cell death and release of tumor antigens) capable of stimulating a secondary, functional systemic immune response (including tumor-specific reactivity in circulating T cells in treatment-refractory patients). PV-10 has been investigated in Phase 1 and 2 clinical trials in 130 patients with melanoma; an expanded access protocol accrued an additional 180 melanoma patients.

Materials and methods: PV-10 is currently under clinical investigation in two melanoma studies. Phase 3 study PV-10-MM-31 (NCT02288897), an international multicenter, randomized controlled trial (RCT), is assessing effectiveness of PV-10 compared to the investigator’s choice of systemic chemotherapy or intralesional oncolytic viral therapy in up to 225 patients with locally advanced cutaneous melanoma (AJCC Stage IIIB to IV M1a). The primary endpoint is progression-free survival (PFS) assessed via RECIST 1.1. Phase 1b/2 combination study PV-10-MM-1201 (NCT02557321), an international multicenter, open-label, sequential phase study, is assessing safety and efficacy of PV-10 in combination with systemic immune checkpoint inhibition. Stage IV metastatic melanoma patients with at least one injectable cutaneous or subcutaneous lesion who are candidates for pembrolizumab are eligible for study participation. In the Phase 1b portion of the study, up to 24 subjects will receive the combination (i.e., PV-10 + SoC) with PFS and objective response (OR) as key secondary endpoints. In the Phase 2 portion of the study up to 120 study participants will be randomized 1:1 to receive either the combination or pembrolizumab alone (i.e., PV-10 + SoC vs SoC) with PFS as the primary endpoint.

Results: Both studies are currently enrolling patients. The Phase 3 study is open at centers in the USA, AUS, Italy and Germany; additional regulatory approval has been received in Mexico, with approval pending in France, Poland and Argentina. The Phase 1b study is open at centers in the USA and AUS. To date, no unexpected safety signals have been observed in either study, and Phase 2 of the combination study is expected to begin in early 2018. Preliminary efficacy data from Phase 1b of the combination trial-in-progress will be presented.

Conclusion: Pivotal testing of single agent PV-10 is ongoing. Conclusion of Phase 1b testing of PV-10 in combination with checkpoint inhibition is anticipated to lead to Phase 2 randomized testing in 2018.
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1352-z