A phase II study of intravenous reolysin (wild-type reovirus) in the treatment of patients with bone and soft tissue sarcomas metastatic to the lung

Abstract

10568 Background: Reolysin (reovirus serotype 3) is a Dearing strain, naturally occurring, ubiquitous, non-enveloped human reovirus. The community-acquired infection is mild and limited to the upper respiratory and GI tract. The virus inhibits the double-stranded RNA- activated protein kinase (PKR) and replicates specifically in transformed cells possessing an activated Ras pathway producing lysis. In in vitro and in vivo studies in Ewing’s sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma cell lines revealed significant antitumor activity. Methods: This phase II open-label, single agent study was designed to characterize the efficacy and safety of reolysin given IV every 28 days (4 weeks) in patients (pts) with bone or soft tissue sarcoma with lung metastasis using a Simon two-stage design. 14 pts will be enrolled in the first stage and up to a total of 56 pts in the second stage if at least 1 pt in the first stage experiences partial response or stable disease for at least 6 months. Results: Since July 2007, 10 pts (pts) age 28 -70 (median 51) were enrolled (6 females and 4 males) and received a total of 23 cycles (range 2–5). The tumor types included malignant fibrous histiocytoma 3 pts, osteosarcoma 3 pts, leiomyosarcoma 2 pts, synovial sarcoma 1 pt, and undifferentiated round cell sarcoma 1 pt. All pts had performance status 1 (7 pts) or 0 (3 pts). Eight pts received prior chemotherapy, radiotherapy, biologic agents or combinations for their metastatic disease. Side effects were mild to moderate (grade 1–2) and included mainly constitutional symptoms fever, chills, arthralgia, fatigue in all pts. Two pts experienced respiratory side effects such as cough and SOB and 2 pts had diarrhea. Hematologic side effects were rare and included grade 2–3 neutropenia (3 pts) and grade 2 thrombocytopenia (2 pts). One pt experienced grade 2 AST elevation. 8 pts are evaluable for response to date: 3 pts had SD (5+, 4 and 2+ months). Four pts had PD. Two pts are too early in the study for tumor evaluation. Conclusions: Reolysin is well tolerated and shows promise for the treatment of metastatic sarcoma. Accrual is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncolytics Biotech, Inc. Oncolytics Biotech, Inc Oncolytics Biotech, Inc