Immunological impact of canerpaturev (C-REV, formerly HF10), an oncolytic viral immunotherapy, with or without ipilimumab (Ipi) for advanced solid tumor patients (pts).

Abstract

2610 Background: C-REV, an oncolytic, spontaneous mutant of Herpes Simplex Virus type 1 (HSV-1), is a cancer immunotherapy agent that combine direct tumor cell killing with immune modulation. A phase I study for solid tumors with cutaneous and/or superficial lesions treated with C-REV monotherapy and a phase II study for unresectable or metastatic melanoma treated with C-REV and Ipi combination therapy were conducted. Immune status of cancer pts before and after administration of C-REV with/without Ipi has been unclear. Methods: A phase I study (n = 6) included solid tumor pts with cutaneous and/or superficial lesions treated with C-REV monotherapy (1 x 106 and 1 x 107 TCID50/mL/dose; 4 injections q2-4wk). In phase II study (n = 28), C-REV (1 x 107 TCID50/mL/dose; 4 injections q1wk; then up to 15 injections q3wk) was injected into each tumor for advanced melanoma pts. Four Ipi infusions (3 mg/kg) were administered at q3wk. Immune-monitoring was conducted before and after treatment in tumor microenvironment usingpaired biopsy samples by multiplex immunohistochemistry (mIHC) and in peripheral blood by flow cytometry (FCM). Results: In the phase I study, significant infiltrations of CD8+and CD4+ T cells were observed at tumor local site statistically in three pts (60%) among five pts. In the phase II study, FCM of peripheral blood (n = 10) showed that the responders (irSD, n = 7, 70%) tend to express the higher levels of ICOS on CD4+ T cells as a pharmacodynamic biomarker of ipi monotherapy reported previously (Ng Tang D, et al. Cancer Immunol Res. 2013) and lower levels of PD-L1 on monocyte after two months of treatment. Moreover, mIHC analysis of paired tumor biopsy samples (n = 11) revealed that five pts (45%) among 11 pts were confirmed persistent infection of C-REV at the injected site by qPCR. Disease control rate of pts with the virus DNA detected on Days 85/169 was higher than that without it (100% [n = 5, irPR; 1, irSD; 4] vs. 33% [n = 6, irSD; 2, irPD; 4]). Furthermore, median OS of pts with or without the DNA detected was 342 or 251 days respectively. Conclusions: Our results suggest C-REV injection in the tumor local site have potential to enhance systemic immune response of Ipi. Clinical trial information: NCT03153085.