To different tumors and antigens without having the need to have to manipulate the viral backbone. A phase I/II clinical trial is presently below preparation.P318 A phase II Cadherin-23 Proteins Biological Activity multicenter trial to evaluate efficacy and safety of HF10 oncolytic virus immunotherapy and ipilimumab in individuals with unresectable or metastatic melanoma Robert HI Andtbacka1, Merrick Ross2, Sanjiv Agarwala3, Kenneth Grossmann1, Matthew Taylor4, John Vetto5, Rogerio Neves6, Adil Daud7, Hung Khong1, Stephanie M Meek8, Richard Ungerleider9, Scott Welden9, Maki Tanaka10, Matthew Williams11 1 University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA; two Univesity of Texas MD Anderson Cancer Center, Houston, TX, USA; 3St. Luke’s Hospital, Easton, PA, USA; 4Oregon Overall health Science University, Portland, OR, USA; 5Knight Cancer Institute, Oregon Wellness and Science University, Portland, OR, USA; 6Pennsylvania State University, GM-CSF R alpha Proteins custom synthesis Hershey Cancer Institute, Hershey, PA, USA; 7UCSF Helen Diller Household Extensive Cancer Center, San Francisco, CA, USA; 8University of Utah College of Medicine, Salt Lake City, UT, USA; 9Theradex, Princeton, NJ, USA; 10Takara Bio, Inc., Otsu Shiga, Japan; 11University of Utah, Salt Lake City, UT, USA Correspondence: Scott Welden ([email protected]) Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):PJournal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):Page 170 ofBackground HF10, an attenuated, replication-competent mutant strain of herpes simplex virus form 1 (HSV1), is usually a promising new oncolytic viral immunotherapy. HF10 (intratumoral injection) shows activity in injected lesions and uninjected metastatic lesions. An ongoing phase II study in melanoma patients (pts) is assessing no matter whether the combination of HF10 along with the immune checkpoint inhibitor ipilimumab (ipi) enhances the antitumor effect of HF10. Procedures Ipi na e pts with stage IIIB, IIIC or IV unresectable melanoma have been enrolled. HF10 was administered intratumorally into single or multiple tumors (1×107 TCID50/mL, up to 5 mL/dose); four injections qwk; then as much as 15 injections q3wk. Ipi was administered intravenously (three mg/kg), q3wk for four doses. Tumor responses (irRC) have been assessed at 12, 18, 24, 36, and 48wks. Greatest Overall Response Rate (BORR) was determined at 24wks. Serial peripheral blood and tumor biopsies were obtained and analyzed for adjustments in cytokines, immune profile and tumor microenvironment. Herein we present the safety, efficacy, and preliminary correlative study final results. Final results In total, 46 pts have been enrolled, of which 20 had been stage IIIB, 43 stage IIIC, and 37 stage IV melanoma. Most HF10-related adverse events (AEs) have been G2, equivalent to HF10 monotherapy. No DLTs were reported; three G4 AEs reported, all not remedy associated. 30.four had G3 AEs. HF10-related G3 AEs (n = three) had been left groin discomfort, thromboembolic event, lymphedema, hypoglycemia, and diarrhea. Of 44 efficacy evaluable pts, preliminary BORR at 24 wks was 42 and all round study BORR which includes those following 24 wks was 50 (20 CR, 30 PR) using a disease manage price of 68 . Of 15 evaluable stage IV pts, 8 (53 ) pts had been responders. In 24 therapy na e pts BORR was 58 (21 CR, 37 PR) and in 20 pts who had failed 1 therapies, BORR was 40 (20 CR, 20 PR). Preliminary serial peripheral blood analyses demonstrated in 75 of responders a sustained 2 fold induction of your Th1 cytokines IFN-gamma and/or TNF-alpha in comparison with baseline at day 0. In contrast, 12 of non-responders demonstrated equivalent induction. F.