title: Phase I clinical trial of sipuleucel-T combined with escalating doses of ipilimumab in progressive metastatic castrate-resistant prostate cancer.
abstract: BACKGROUND
  Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic.
  
  
  METHODS
  Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T. Three patients were evaluated at each level. Cancer-specific immunoglobulins directed at granulocyte-macrophage-colony-stimulating factor/prostatic acid phosphatase (PAP) fusion protein (PA2024) and PAP were measured prior to SIP-T, after SIP-T, 1 week after IPI, every other month for 5 months, then every 3 months for an additional 12 months.
  
  
  RESULTS
  Adverse events of SIP-T were consistent with previous reports. IPI only caused a transient grade 1 rash in one patient. Median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Eight men had bone metastases and one had lymph node metastasis. Statistically significant increases in serum immunoglobulin G (IgG) and IgG-IgM specific for PA2024 and PAP occurred after SIP-T. An additional statistically significant increase in the aforementioned immunoglobulins - above the levels achieved by SIP-T - occurred after IPI. Median clinical follow-up was 36 months (range: 26-40). Three patients died from progressive disease after 9, 18, and 20 months. Out of the remaining six patients, five of them needed further treatment that included abiraterone acetate, enzalutamide, radium-223 dichloride, and spot radiation. One patient had an undetectable PSA, who did not receive any other treatment except spot radiation. Median PSA at last follow-up for the surviving patients was 3.8 (range: 0.6-7.47).
  
  
  CONCLUSIONS
  In this small trial, the addition of IPI to SIP-T was well tolerated. IPI increased immunoglobulins specific for the PA2024 protein and PAP above the level achieved with SIP-T alone.
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Mark
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Yep
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Micah
authors.initials: M
authors.lastname: Chancey
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Ken
authors.initials: K
authors.lastname: Chau
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Turner
authors.affiliation: Prostate Oncology Specialists, Inc., Marina del Rey, CA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lam
authors.affiliation: The Sidney Kimmel Cancer Center; The James Buchanan Brady Urological Institute, John Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
keywords: immune therapy; ipilimumab; prostate cancer; sipuleucel-T