Results from phase I study of the oncolytic viral immunotherapy agent canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer.

Abstract

325 Background: Canerpaturev (C-REV, formerly HF10) is an oncolytic, spontaneous mutant Herpes Simplex Virus type 1, and is one of immunotherapies that combine direct tumor cell killing with immune modulation. The purpose of this study is to determine the recommended dose of C-REV in combination with chemotherapy (Gemcitabine + Nab-paclitaxel; G-nP) in Japanese patients with stage III or IV unresectable pancreatic cancer. We report the safety and antitumor activity data of this study. Methods: This study was a “3 + 3” design with a 2-dose escalation scheme evaluating 2 doses of C-REV. The subjects received C-REV at 1x106 or 1x107 TCID50/mL (up to 2mL, depending on tumor size) intratumorally by EUS-guidance at a 2-week interval in addition to 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel by intravenous infusion on days 1, 8, and 15 of a 4-week cycle. The study treatment could continue up to 1 year if eligible for injection. The primary endpoint was Dose Limiting Toxicity (DLT); the secondary endpoints were adverse events (AEs) assessed per NCI CTCAE v4.0, Best Overall Response Rate (BORR) at 16-week by RECIST and progression-free survival. Results: Six patients (pts) were enrolled and treated: 33% (2/6) men, age range 63 to 72 yrs, disease stage 33% III, 66% IV. Of 6 safety evaluable pts, no DLTs were reported. 16% (1/6) pt(s) had C-REV-related ≥ G3 AE, and it was acute pancreatitis (G3). G-nP-related ≥ G3 AEs observed in more than 2 pts were neutropenia (50%), and the majority of ≥ G3 AEs were similar as the AEs previously reported in G-nP therapy. As of 01 Sep 2018, of the 6 efficacy evaluable pts, BORR at 16-week was 66% (4 PR). Disease control rate was 100% (2 SD), and 1 of 2 SD pts continues the study treatment. We will present the updated data. Conclusions: The recommended dose was determined as 1x107 TCID50/mL. The combination of C-REV and the standard chemotherapy demonstrated a favorable benefit/risk profile and encouraging antitumor activity in Japanese patients with unresectable pancreatic cancer. Clinical trial information: NCT03252808.