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

作者：Sanjiv S. Agarwala, Merrick I. Ross, Jonathan S. Zager, Keisuke Shirai, Richard Essner, B. Mark Smithers, Victoria Atkinson, Eric A. Wachter · 发表于：Journal of Clinical Oncology · 年份：2019 · DOI：10.1200/jco.2019.37.15_suppl.9559 · 被引用次数：21 · 研究领域：CAR-T cell therapy research、Cancer Research and Treatments、Cancer Immunotherapy and Biomarkers

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 o...