Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

Lancet Oncol. 2012 May;13(5):501-8. doi: 10.1016/S1470-2045(12)70006-2. Epub 2012 Feb 10.


Background: Therapeutic cancer vaccines have shown activity in metastatic castration-resistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic T-lymphocyte-associated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigen-presenting cells. We aimed to assess the safety and tolerability of ipilimumab in combination with a poxviral-based vaccine targeting prostate-specific antigen (PSA) and containing transgenes for T-cell co-stimulatory molecule expression, including CD80.

Methods: We did a phase 1 dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipilimumab in combination with a fixed dose of the PSA-Tricom vaccine. Patients with mCRPC received 2×10(8) plaque-forming units of recombinant vaccinia PSA-Tricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1×10(9) plaque-forming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. This study is registered with ClinicalTrials.gov, number NCT00113984.

Findings: We completed enrolment with 30 patients (24 of whom had not been previously treated with chemotherapy) and we did not identify any dose-limiting toxic effects. Grade 1 and 2 vaccination-site reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immune-related adverse events. Grade 3 or 4 immune-related adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immune-related adverse events (two patients), and grade 4 neutropenia (one patient). Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapy-naive, 14 (58%) had PSA declines from baseline, of which six were greater than 50%.

Interpretation: The use of a vaccine targeting PSA that also enhances co-stimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC.

Funding: US National Institutes of Health.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD / immunology
  • Antineoplastic Agents / therapeutic use*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunotherapy, Active
  • Ipilimumab
  • Male
  • Middle Aged
  • Orchiectomy
  • Poxviridae* / immunology
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / secondary
  • Prostatic Neoplasms / therapy*
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use*


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antineoplastic Agents
  • Cancer Vaccines
  • Ipilimumab
  • Viral Vaccines
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT00113984