Percutaneous hepatic injection of rose bengal disodium (PV-10) in metastatic uveal melanoma.

Abstract

3143 Background: PV-10 is a small molecule autolytic immunotherapy in clinical development for treatment of solid tumors. When administered by intralesional (IL) injection, PV-10 can produce immunogenic cell death that may induce a T cell-mediated immune response against treatment refractory and immunologically cold tumors. Given this mechanism of action and clinical data that metastatic uveal melanoma (MUM) generates low response rates to immune checkpoint blockade (CB), we investigated treatment of MUM with percutaneously-delivered PV-10. Methods: This open-label Phase 1 basket study (NCT00986661) is evaluating the safety, tolerability, and preliminary efficacy of intralesional PV-10 in patients (pts) with solid tumors of the liver. PV-10 is injected into one or more designated hepatic tumor(s) with a maximum sum of diameters ≤4.9 cm. Response assessments using 2D EASL criteria are performed at Day 28, then every 3 months. Pts with additional injectable tumors are eligible to receive further PV-10 after Day 28. Pts can receive standard of care CB immunotherapy during treatment with PV-10. Results: As of February 1, 2020, the initial cohort of 15 pts with MUM to the liver was fully enrolled. Pts had received at least 1 IL injection of PV-10, with an average of 2 hepatic lesions injected per pt (range 1-4). Of these, 4 pts were refractory to prior CB. Three pts received PV-10 alone, 3 received PV-10 + anti-PD-1 and 9 received PV-10 + anti-PD-1 + anti-CTLA-4. Adverse events (AEs) were consistent with established patterns for PV-10 and CB: AEs attributed to PV-10 were transient and included 3 cases of Grade 3/4 transaminitis that resolved within 72 hrs, injection site pain, photosensitivity, and pink discoloration of skin, urine or feces; AEs attributed to CB included nausea, decreased WBC, and fatigue. Response assessments on 24 injected tumors were: 2 complete response (8%), 7 partial response (29%) and 11 stable disease (46%), per 2D EASL. Among the 4 CB-refractory pts, median overall survival (OS) was 9.2 months (range 5.3 - 11.4 months, with 2 pts alive at 5.3 months each), while among the 11 CB-naïve pts OS was undefined (range 0.5 - 21.9+ months, with 1 death at 7.9 months). Pts receiving PV-10 alone (1 CB-refractory, 2 naïve) achieved a median OS of 7.9 months with one CB-naïve pt alive with partial overall response at 21.9 months. Conclusions: Response indicative of regression or stabilization in a majority (83%) of injected lesions is encouraging in a disease of major unmet need. Enrollment and follow-up for safety, duration of response and survival are ongoing. Clinical trial information: NCT00986661 .