729. Phase I Trial of Intraperitoneal (IP) Administration of a Measles Virus (MV) Strain Expressing the Human Carcinoembryonic Antigen (CEA) in Ovarian Cancer Patients

Abstract

Top of pageAbstract Background: Edmonston vaccine strains of MV have significant antitumor activity against ovarian cancer xenografts (Peng et al, Cancer Res, 2002). Oncolytic selectivity is due to overexpression of the MV CD46 receptor in ovarian cancer cells. Furthermore, engineering the virus to express the marker peptide CEA (MV-CEA) allows real time monitoring of viral gene expression/ propagation in vivo. Methods: We are conducting a Phase I trial of MV-CEA in patients (pts) with recurrent, taxol and platinum refractory ovarian or primary peritoneal carcinoma. Eligible pts should have protective anti-MV antibody (ab) titers and normal CEA levels. A standard phase I cohorts of three statistical design is employed. MV-CEA is administered IP via a port-a-cath, q 4 wks for up to 6 cycles. Results: To date, 12 pts have received viral doses from 103 to 106 TCID50. No dose-limiting toxicity has been observed. Most common toxicities included grade 1|[ndash]|2 nausea (4 pts); grade 1|[ndash]|2 fatigue (4 pts); grade 1 fever (3 pts); grade 1 abdominal pain (2 pts). One pt had grade 1|[ndash]|3 arthralgias in cycles 4|[ndash]|6. There was no treatment induced immunosuppression as assessed by DTH, CD4, CD8, immunoglobulin and complement levels, no significant increase in the titers of anti-MV abs in serum or ascites in response to treatment, and no development of anti-CEA abs. Viral genomes were detected in the peripheral blood mononuclear cells of 2 asymptomatic pts by QRT-PCR. No CEA elevation in the serum was observed in the dose range tested, and there was no viral shedding in urine or mouth gargle specimens. Testing of pt tumor samples for CD46 by IHC demonstrated overexpression of the target receptor in 7/8 pts. Best objective response was stable disease (2|[ndash]|8 mo duration) in 5 pts, while 3 pts had significant decrease in CA125 levels, of 44%, 72%, and 78%, respectively. Conclusions: In this first human application of an engineered oncolytic MV strain, we have observed excellent tolerance after repeat IP administration of the virus. Despite the low doses employed so far, there is early evidence of biologic activity. Dose escalation continues to the target dose of 109 TCID50.