Phase 1b study of PV-10 and anti-PD-1 in advanced cutaneous melanoma.

Abstract

9559 Background: PV-10 (rose bengal disodium) is a small molecule oncolytic immunotherapy in development for solid tumors, where intralesional injection can yield immunogenic cell death and tumor-specific reactivity in circulating T cells. It has been administered as a single agent to over 300 cutaneous melanoma patients (pts) in Phase 1-3 testing and under expanded access. Methods: Study PV-10-MM-1201 (NCT02557321) is a Phase 1b/2 study of PV-10 in combination with anti-PD-1 (pembrolizumab) for patients with advanced cutaneous melanoma (Stage IIIB-IV M1c). Patients must have at least 1 injectable lesion and be candidates for pembrolizumab. In Phase 1b pts receive combination treatment q3w for 5 cycles then pembrolizumab alone for up to 24 months; the primary endpoint is safety and tolerability with objective response rate (ORR) and progression free survival (PFS) key secondary endpoints (by RECIST 1.1 after 5 cycles then q12w). Results: Full accrual of the Main Cohort of Phase 1b was reached in April 2018, with an intent-to-treat population of 23 pts (3 IIIC/IIID, 8 M1a, 7 M1b, 5 M1c; median age 70 years, range 28-90). Treatment-Emergent Adverse Events (TEAEs) were consistent with established patterns for each drug, principally Grade 1-2 injection site reactions attributed to PV-10 and Grade 1-3 immune-mediated reactions attributed to pembrolizumab, with no significant overlap or unexpected toxicities: 6 Grade 1-2 TEAEs were attributed to the combination in 6 pts. Response of injected lesions was 77% CR (3% PR) achieved after a median of 3 injections / lesion administered over a median of 4 treatment cycles of PV-10 (range 1-5). Most pts had extensive uninjected tumor burden, and a best overall response of CR was achieved in 9% of pts (1 each M1a and M1b), with 57% of pts achieving PR (including 4 of 5 M1c pts). Response assessment is ongoing; final ORR and PFS data for the Main Cohort will be presented along with correlative T cell data. Conclusions: The primary endpoint for Phase 1b was met, with acceptable safety and tolerability of the combination and no unexpected safety issues identified. Two Phase 1b Expansion Cohorts (24 pts each) have been opened to pts refractory to prior checkpoint inhibition and pts with in-transit or satellite disease. Clinical trial information: NCT02557321.