Abstract 1123P
Background
PV-10 (10% rose bengal disodium for injection) is a small molecule autolytic immunotherapy in development for solid tumors; intralesional (IL) injection can yield immunogenic cell death and induce tumor-specific reactivity in circulating T cells. Functional T cell response may be enhanced through combination with immune checkpoint blockade (CB).
Methods
PV-10-MM-1201 (NCT02557321) is a phase 1b/2 study of IL PV-10 in combination with systemic anti-PD-1 (pembrolizumab, “pembro”) for patients (pts) with advanced cutaneous melanoma; pts must have at least 1 injectable lesion and be candidates for pembro. The combination is administered q3w for 5 cycles followed by pembro alone q3w for up to 24 months. The primary endpoint is safety and tolerability, with objective response rate (ORR) and progression-free survival (PFS) as key secondary endpoints (assessed by RECIST 1.1 after 5 cycles then q12w). Immune correlative assessments are being performed on a subgroup of pts.
Results
We report initial results of an expansion cohort of melanoma pts refractory to CB, an indication with unmet clinical need. Pts (N = 13: 1 Stage IIIC, 1 IIID, 4 M1a, 2 M1b, 3 M1c, 2 M1d; median age 77 years, range 54-90) had one or more prior lines of CB (2 pts were refractory to CTLA-4, 4 to PD-1 and 7 to CTLA-4 and PD-1). Adverse events were consistent with established patterns for each drug. This initial group achieved an ORR of 31% (PRs among 4 IIIC, IIID, M1a, and M1d pts), while 2 pts (M1a and M1c) achieved SD, for a disease control rate of 46%. Four pts have completed correlative assessment: 2 of these pts exhibited increased High Mobility Group Box 1 (HMGB1), a Damage Associated Molecular Pattern (DAMP) molecule associated with activation of dendritic cells, in post-PV-10 serum; and 1 pt (M1a refractory to CTLA-4 and PD-1) also exhibited increased T cell reactivity to HLA-matched tumor 7 days after initiation of PV-10 treatment that preceded achieving a durable PR.
Conclusions
Acceptable safety and tolerability were observed, supporting ongoing enrollment. Pharmacodynamic assessments are consistent with the immune-mediated mechanism of action of PV-10 in this CB-refractory population.
Clinical trial identification
NCT02557321.
Editorial acknowledgement
Legal entity responsible for the study
Provectus Biopharmaceuticals, Inc.
Funding
Provectus Biopharmaceuticals, Inc.
Disclosure
E. Wachter: Leadership role, Full/Part-time employment: Provectus Biopharmaceuticals. All other authors have declared no conflicts of interest.