To distinctive tumors and antigens with no the need to manipulate the viral backbone. A phase I/II clinical trial is at present beneath preparation.P318 A phase II multicenter trial to evaluate efficacy and PI3K Modulator Accession safety of HF10 oncolytic virus ImmunoTherapy and ipilimumab in sufferers 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; 2 Univesity of Texas MD Anderson Cancer Center, Houston, TX, USA; 3St. Luke’s Hospital, Easton, PA, USA; 4Oregon Wellness Science University, Portland, OR, USA; 5Knight Cancer Institute, Oregon Overall health and Science University, Portland, OR, USA; 6Pennsylvania State University, Hershey Cancer Institute, Hershey, PA, USA; 7UCSF Helen Diller Household Extensive Cancer Center, San Francisco, CA, USA; 8University of Utah School 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, four(Suppl 1):PJournal for ImmunoTherapy of Cancer 2016, four(Suppl 1):Page 170 ofBackground HF10, an attenuated, replication-competent mutant strain of herpes simplex virus type 1 (HSV1), is often 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 sufferers (pts) is assessing whether or not the combination of HF10 and also the immune checkpoint inhibitor ipilimumab (ipi) enhances the antitumor impact 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 many tumors (1×107 TCID50/mL, as much as five mL/dose); four injections qwk; then as much as 15 injections q3wk. Ipi was administered intravenously (3 mg/kg), q3wk for four doses. Tumor responses (irRC) had been assessed at 12, 18, 24, 36, and 48wks. Most effective All round Response Price (BORR) was determined at 24wks. Serial peripheral blood and tumor biopsies had been obtained and analyzed for changes in cytokines, immune profile and tumor microenvironment. Herein we present the security, efficacy, and preliminary correlative study results. 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) were G2, related to HF10 monotherapy. No DLTs had been reported; three G4 AEs reported, all not treatment connected. 30.four had G3 AEs. HF10-related G3 AEs (n = three) had been left groin pain, thromboembolic event, lymphedema, hypoglycemia, and diarrhea. Of 44 efficacy evaluable pts, preliminary BORR at 24 wks was 42 and general study BORR including those just after 24 wks was 50 (20 CR, 30 PR) having a illness control price of 68 . Of 15 evaluable stage IV pts, eight (53 ) pts had been responders. In 24 remedy 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 two fold induction in the Th1 cytokines IFN-gamma and/or TNF-alpha compared to PPARĪ± Activator custom synthesis baseline at day 0. In contrast, 12 of non-responders demonstrated comparable induction. F.
