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Results from ADVANCE: A phase I/II open-label non-randomised safety and efficacy study of the viral vectored ChAdOx1-MVA 5T4 (VTP-800) vaccine in combination with PD-1 checkpoint blockade in metastatic prostate cancer
Tuthill, M. Cappuccini, F. Carter, L. Pollock, E. Poulton, I. Verrill, C. Evans, T. Gillessen, Silke Attard, G. Protheroe, A.
Tuthill, M.
Cappuccini, F.
Carter, L.
Pollock, E.
Poulton, I.
Verrill, C.
Evans, T.
Gillessen, Silke
Attard, G.
Protheroe, A.
Citations
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Abstract
Background: New therapeutic antigen-specific approaches are required to generate
and sustain therapeutic immune responses against tumour specific antigens in men
with advanced prostate cancer. We have previously reported efficacy data on a novel
vaccine based on two replication-deficient viruses, chimpanzee adenovirus (ChAdOx1)
and MVA, targeting an oncofetal self-antigen 5T4, administered as a single agent and
in combination with anti-PD-1 in mouse tumour models. Based on encouraging safety
and exceptional T cell immunogenicity of the VANCE study (NCT02390063), the phase
I/II trial, ADVANCE (NCT03815942) was undertaken to test the vaccine safety and
efficacy in combination with PD-1 blockade in metastatic castrate-resistant prostate
cancer (mCPRC).
Methods: ADVANCE recruited mCRPC patients with disease progression on antiandrogen
therapy with either enzalutamide or abiraterone. Patients received 2 cycles
of ChAdOx1-MVA 5T4 (VTP-800) vaccination and three nivolumab infusions. The
primary endpoint is a composite response rate measured as either a 50% reduction of
circulating tumour DNA or a 50% serum PSA decrease from baseline at 24-week
assessment and the maximal response rate. Secondary and exploratory endpoints
include 5T4-specific immune response in the periphery, progression-free and overall
survival and reduction of circulating tumour cells.
Results: 23 patients were recruited (- the trial is now closed to recruitment -) and met
the endpoint for performing the first data analysis. Of 23 mCRPC patients who
received VTP-800 in conjunction with an anti-PD-1, 5 patients (22%) had a >50%
reduction in PSA level at any time point compared to the baseline (median of 88 ng/
ml). VTP-800 and Nivolumab treatment were well tolerated.
Conclusions: VTP-800 and Nivolumab treatment led to a >50% reduction in PSA in
22% of patients in the ADVANCE trial and were well tolerated. Analysis of safety data,
changes in circulated tumour DNA, 5T4-specific immune response in the periphery,
progression-free and overall survival and reduction of circulating tumour cells are
ongoing and will be presented at the meeting.
Description
Date
2020
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Tuthill M, Cappuccini F, Carter L, Pollock E, Poulton I, Verrill C, et al. 682P Results from ADVANCE: A phase I/II open-label non-randomised safety and efficacy study of the viral vectored ChAdOx1-MVA 5T4 (VTP-800) vaccine in combination with PD-1 checkpoint blockade in metastatic prostate cancer. Annals of Oncology. 2020;31:S543-S.