Cancer Immunology, Immunotherapy

, Volume 62, Issue 9, pp 1511–1520 | Cite as

Vaccination of castration-resistant prostate cancer patients with TroVax (MVA–5T4) in combination with docetaxel: a randomized phase II trial

  • Richard Harrop
  • Franklin Chu
  • Nashat Gabrail
  • Sandy Srinivas
  • Daniel Blount
  • Anna Ferrari
Original Article

Abstract

The attenuated vaccinia virus, modified vaccinia Ankara, has been engineered to deliver the tumor antigen 5T4 (TroVax®). Here, we report results from a randomized open-label phase II trial in castration-resistant prostate cancer patients in which TroVax was administered in combination with docetaxel and compared against docetaxel alone. The aim was to recruit 80 patients (40 per arm), but the study was terminated early due to recruitment challenges. Therefore, this paper reports the comparative safety and immunological and clinical efficacy in 25 patients, 12 of whom were treated with TroVax plus docetaxel and 13 with docetaxel alone. 5T4-specific immune responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by CT and bone scan and by quantifying PSA concentrations. TroVax was well tolerated in all patients. Of 10 immunologically evaluable patients, 6 mounted 5T4-specific antibody responses. Patients treated with TroVax plus docetaxel showed a greater median progression-free survival of 9.67 months compared with 5.10 months for patients on the docetaxel alone arm (P = 0.097; HR = 0.31; 95 % CI 0.08–1.24). Importantly, a pre-treatment biomarker previously demonstrated to predict 5T4 immune response and treatment benefit showed a strong association with 5T4 antibody response and a statistically significant association with progression-free survival in patients treated with TroVax plus docetaxel, but not docetaxel alone.

Keywords

Castration-resistant prostate cancer Cancer vaccine 5T4 tumor antigen Biomarker Docetaxel 

Notes

Conflict of interest

Richard Harrop and Daniel Blount wish to disclose that they are employees of Oxford BioMedica, the manufacturer and developer of TroVax®. Franklin Chu, Nashat Gabrail, Sandy Srinivas, and Anna Ferrari have no conflicts of interest to declare.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Richard Harrop
    • 1
  • Franklin Chu
    • 2
  • Nashat Gabrail
    • 3
  • Sandy Srinivas
    • 4
  • Daniel Blount
    • 1
  • Anna Ferrari
    • 5
  1. 1.Oxford BioMedica (UK) Ltd., The Medawar CentreOxford Science ParkOxfordUK
  2. 2.San Bernardino UrologySan BernardinoUSA
  3. 3.Gabrail Cancer Center ResearchCantonUSA
  4. 4.Stanford University Medical CenterStanfordUSA
  5. 5.New York University Cancer InstituteNew YorkUSA

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