TRIOC-A randomised phase II trial to examine MVA-5T4 vaccine in patients with relapsed asymptomatic epithelial ovarian, fallopian tube or primary peritoneal cancer

Abstract

Background: Continued surveillance is often used in patients with ovarian cancer who have asymptomatic relapse. Immunotherapy directed at 5T4, an onco-foetal tumour antigen (TAA) may contain the relapse and delay the need for further chemotherapy. MVA-5T4 (TroVax ) consists of an attenuated Vaccinia Virus (Modified Vaccinia Ankara, MVA) containing the gene encoding for the human TAA, 5T4. We examined whether MVA-5T4 vaccination can delay tumour progression of relapsed ovarian cancer. Methods: The trial started as a double-blind randomised phase II trial with placebo, but an unforeseen interim trial suspension led to limited drug supply, so it later changed to a single arm study. Eligible patients had asymptomatic (CA-125 rise onlyor low volume disease) relapsed ovarian cancer; 6 months since prior chemotherapy and ECOG 0-1. Primary endpoint was progression rate at 25 weeks (PR-25): confirmed progression using RECIST and immune-related response criteria, clinical intervention for symptoms of progression or death. We aimed to detect an improvement in PR from 70% (placebo) to 50% (MVA-5T4). Results: 94 eligible patients were recruited from 12 centres (11/13 to 11/17). There were 69 randomised patients, 25 were added in a single arm study. Median age was 65 years (range 42 to 82), and median time since prior chemotherapy 18 months (7 to 86); median follow up 34 months (2 to 46). 22 patients were withdrawn from trial treatments during the suspension. The PR-25 was similar: 80.0% (MVA-5T4) vs 82.9% (placebo) p-0.74. In the pre-specified per protocol analysis (patients who had 5 treatment injections and were unaffected by trial suspension), the corresponding rates were 78.8% and 90.9%. Median PFS was the same in both arms (3.0 months). Median time to clinical intervention appeared to be improved with MVA-5T4 9.7 (6.7- 14.3) vs 6.1 (5.1-8.6), p-0.14. 27.6% (MVA-5T4) vs 22.9% (placebo) had a grade 3-4 adverse event. QoL was also similar in both arms. Conclusions: MVA-5T4 vaccination in patients with asymptomatic relapse was welltolerated but did not improve the progression rate at 25 weeks. Further immunological analysis to identify subsets of patients who might benefit from MVA-5T4 is ongoing.