Abstract 838P
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 only-or 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and median time since prior chemotherapy 18 months (7 to 86); median follow up 34 months (2 to 46). 22 patients were withdrawn from trial treatments during the suspension.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 well-tolerated 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.
Clinical trial identification
EudraCT: 2011-001836-44.
Editorial acknowledgement
Legal entity responsible for the study
Cancer Research UK & UCL Cancer Trials Centre.
Funding
Oxford Biomedica.
Disclosure
A. Michael: Advisory/Consultancy, Travel/Accommodation/Expenses: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self): Novartis; Honoraria (self): Pfizer. R. Harrop: Full/Part-time employment: Oxford Biomedica. I. McNeish: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Advisory/Consultancy: GSK; Advisory/Consultancy: Carrick Therapeutics; Advisory/Consultancy: Roche; Research grant/Funding (institution): AstraZeneca. R. Lord: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca. D. Blount: Full/Part-time employment: Oxford Biomedica. A.R. Clamp: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Travel/Accommodation/Expenses: Clovis. R. Kristeleit: Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Clovis; Advisory/Consultancy: Basilea; Advisory/Consultancy: InCyte; Advisory/Consultancy: Merck; Advisory/Consultancy: IGEM Therapeutics; Advisory/Consultancy: Sierra Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. S. Nicum: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca. A. Walther: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca. A. Hackshaw: Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies: Roche; Shareholder/Stockholder/Stock options: Thermo Fisher; Shareholder/Stockholder/Stock options: Illumina; Honoraria (self): Boehringer; Honoraria (self): AbbVie; Honoraria (self): Merck /Serono; Honoraria (self): Merck /MSD; Honoraria (self): Daiichi Sankyo; Advisory/Consultancy: GRAIL Inc; Advisory/Consultancy: Abbvie; Honoraria (self): Takeda. J.A. Ledermann: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): MSD/Merck; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Clovis; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): GSK; Honoraria (self): Seattle Genetics; Honoraria (self): Artios; Honoraria (self): Eisai; Honoraria (self): Amgen. All other authors have declared no conflicts of interest.