Vaccination of Renal Cell Cancer Patients with Modified Vaccinia Ankara Delivering Tumor Antigen 5T4 (TroVax) Administered with Interleukin 2: A Phase II Trial

Abstract

Purpose: The attenuated vaccinia virus modified vaccinia ankara (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). TroVax has been evaluated in an open-label phase II trial in metastatic renal cell cancer patients in which the vaccine was administered in combination with interleukin-2 (IL-2). The safety, immunologic, and clinical efficacy of TroVax in combination with IL-2 was determined. Experimental Design: Twenty-five patients with metastatic renal cell cancer were treated with TroVax plus IL-2. 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan. Results: TroVax was well tolerated with no serious adverse event attributed to vaccination. Of 25 intention-to-treat patients, 21 mounted 5T4-specific antibody responses. Two patients showed a complete response for >24 months and one a partial response for >12 months. Six patients had disease stabilization from 6 to >21 months. Median progression-free survival (PFS) and overall survival (OS) were >3.37 months (range, 1.50->24.76) and >12.87 months (range, 1.90->24.76), respectively. A statistically significant relationship was detected between the magnitude of 5T4-specific antibody responses and PFS and OS. Conclusion: TroVax in combination with IL-2 was safe and well tolerated in all patients. The high frequency of 5T4-specific immune responses and good clinical response rate are encouraging and warrant further investigation.