Abstract 1125P
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. Eligibility for the main cohort of phase 1b required pts to have at least 1 injectable lesion, be CB-naïve, and be candidates for pembro. The combination was administered q3w for 5 cycles followed by pembro alone q3w for up to 24 months. The primary endpoint was safety and tolerability, with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) as key secondary endpoints (assessed by RECIST 1.1 after 5 cycles then q12w).
Results
Full accrual of the main cohort was reached in April 2018 and final response assessments were competed in April 2020, with 21 CB-naïve pts (2 IIIC/IIID, 8 M1a, 7 M1b, 4 M1c; median age 69 years, range 28-82) receiving at least 1 dose of PV-10 and pembro (2 enrolled pts with prior CB treatment are not included here). Treatment-Emergent Adverse Events 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 pembro, with no significant overlap or unexpected toxicities. Among this predominantly Stage IV population, an ORR of 67% was achieved, with 10% CR (1 pt each with M1a and M1b disease) and 57% PR (including all M1c pts). Median PFS was estimated at 11.7 months. Median OS was not reached (landmark overall survival was 92% and 62% at 1 and 2 years, respectively); disease-specific survival was 100% and 65% at 1 and 2 years, respectively.
Conclusions
The primary endpoint for phase 1b was met, with acceptable safety and tolerability and no unexpected safety issues identified. Two phase 1b expansion cohorts (24 pts each) are enrolling pts refractory to prior CB and pts with in-transit or satellite disease.
Clinical trial identification
NCT02557321.
Editorial acknowledgement
Legal entity responsible for the study
Provectus Biopharmaceuticals, Inc.
Funding
Provectus Biopharmaceuticals, Inc.
Disclosure
E. Wachter: Shareholder/Stockholder/Stock options, Full/Part-time employment: Provectus Biopharmaceuticals. All other authors have declared no conflicts of interest.