A Phase 2 Study of Intravenous REOLYSIN® (Wild-Type Reovirus) in the Treatment of Patients With Bone and Soft Tissue Sarcomas Metastatic to the Lung

Trial Information

A Phase 2 Study of Intravenous REOLYSIN® (Wild-Type Reovirus) in the Treatment of Patients With Bone and Soft Tissue Sarcomas Metastatic to the Lung

Sarcomas are uncommon mesenchymal malignancies that encompass a variety of tumors of soft
tissue or bone. Included in this study are patients with osteosarcoma, Ewing sarcoma family
tumors, malignant fibrous histiocytoma, synovial sarcoma, leiomyosarcoma and fibrosarcoma.
Patients with these lesions presenting with metastatic disease remain largely incurable. In
all sarcomas, the lungs are by far the most frequent site of metastases.

There is a need for new therapies that have activity against these types of sarcomas.
REOLYSIN® is an unmodified oncolytic reovirus which replicates selectively in ras
transformed cells causing cell lysis. Activating mutations in ras or mutations in oncogenes
signaling through the ras pathway may occur in as many as 80% of human tumors. Such
mutations have been described in many of the common sarcomas of childhood and adults.
REOLYSIN® demonstrated excellent anti-tumor activity in vitro and in vivo in childhood
sarcoma cell lines.

Further supporting the development of REOLYSIN® in the context of sarcomas as detailed in
this study, is the fact that sarcomas resistant or refractory to conventional chemotherapy
may remain clinically responsive to viral therapy. Sarcoma patients with pulmonary
metastases may be especially suitable for studies with REOLYSIN® due to rapid selective
uptake of the virus by the lungs.

This Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN® given
intravenously over 5 days every 4 weeks in patients with bone and soft tissue sarcomas
metastatic to the lung. Safety data, including laboratory parameters and adverse events,
will be collected for all patients in order to determine the toxicity and reversibility of
toxicity of REOLYSIN® therapy. Response will be assessed using radiographic imaging every 2
cycles of therapy.

OBJECTIVES:

1. To measure tumor responses and duration of response, and describe any evidence of
antitumor activity of intravenous multiple dose REOLYSIN® in patients with bone and
soft tissue sarcomas metastatic to the lung.

2. To evaluate safety of intravenous multiple dose REOLYSIN®.