PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma

This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for pembrolizumab (both treatment naïve patients and treatment refractory patients who have failed to achieve a complete or partial response to or previously progressed on one or more checkpoint inhibitor) will be eligible for study participation. In the Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).

Phase 1b. Up to 24 eligible subjects will be enrolled in an initial cohort in the Phase 1b portion of the study (Main Cohort). Up to an additional 24 eligible subjects who have failed to achieve a complete or partial response to or progressed on prior checkpoint inhibition will be enrolled in a first expansion cohort (Expansion Cohort 1). Up to an additional 24 eligible subjects with Stage III unresectable, in-transit or satellite melanoma will be enrolled in a second expansion cohort (Expansion Cohort 2). Each subject in each Phase 1b cohort will receive the combination of IL PV-10 and pembrolizumab. Phase 2. A total of an estimated 120 eligible subjects will be randomized in a 1:1 ratio to the two treatment arms (i.e., PV-10 + pembrolizumab or pembrolizumab alone) in the Phase 2 portion of the study. This number of subjects may be modified based on emerging evidence of preliminary efficacy and effect size from the Phase 1b and initial Phase 2 portions of the study. Subjects assigned to receive PV-10 in Phase 1b and 2 will receive initial IL PV-10 to their injectable lesions commencing on study Day 1 for up to 12 weeks (i.e., investigational Treatment Phase of the study). PV-10 may be re-administered at 21-day (3-week) intervals during the Treatment Phase of the study to any remaining, uninjected injectable lesions until all injectable lesions have been injected. Lesions that fail to exhibit complete ablation may be re-injected on this schedule. Pembrolizumab will be administered at 21-day (3-week) intervals per prescribing information (label) commencing on study Day 1 for up to 24 months or until disease progression, toxicity requiring discontinuation of study treatment or study termination.