A phase II study of an oncolytic herpes simplex virus 2 and an anti-PD-1 antibody in patients with advanced sarcoma.

11571 Background: OH2 is an attenuated oncolytic Herpes Simplex-2 Virus expressing GM-CSF. In a phase I/II open-label clinical trial OH2 was safe and efficacious as monotherapy. When combined with HX008, a humanized anti-PD-1 antibody, OH2 demonstrated a disease control rate of 50% in solid tumors (1). Here, we present the efficacy results observed in a sarcoma-specific expansion cohort of the trial. Methods: Patients refractory to ≥1 prior line of systemic therapy were allocated to a monotherapy group receiving intratumoral OH2 once every 2 weeks and a combination group receiving i.t. OH2 and HX008 (i.v) every 3 weeks. The primary endpoint was best objective response rate (ORR, per RECIST v 1.1). Secondary endpoints were disease control rate (DCR), progression free survival (PFS), overall survival (OS), duration of response (DOR) and adverse effects (AEs). Results: 26 patients were enrolled in the phase II trial, 7 in the monotherapy group and 19 in the combo group. Median age was 52 years, with 65.4% females. 50% had received ≥3 prior lines of therapy, whereas 30.7% had prior lines of immunotherapy. 25 patients were evaluable for efficacy (1 withdrew). ORR was 0% and 16.7%; DCR 14.3% and 50.0%; median PFS 1.4 and 2.1 months, and median OS 4.5 and 22.3 months, for the monotherapy and combo groups, respectively. In the combo group we observed 1 CR and 2 PRs, in which the DOR was 4.2, 5.6 and 11.1 months (Table). Angiosarcoma and fibrosarcoma patients experienced clinical benefit with durable disease control, with one angiosarcoma patient remaining in study for >1 year. Treatment was well tolerated with most common AEs being grade I and II, including GGT elevation (26.9%), fever (23.1%), neutropenia (19.2%), weight loss (15.4%), LDH elevation (15.4%), and anemia (15.4%). Conclusions: OH2 and HX008 demonstrated goodsafety and encouraging anti-tumor activity in a phase II sarcoma cohort. Further clinical investigation of this combination is warranted. 1. Zhang et al, 2021; PMID: 33837053. Table: see text