title: Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.
abstract: BACKGROUND
  CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC).
  
  
  METHODS
  Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07).
  
  
  CONCLUSIONS
  CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509).
  
  
  BACKGROUND
  NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.
authors.affiliation: University of Washington Medical Center, Seattle, WA USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Gray
authors.affiliation: Northside Hospital, Atlanta, GA USA.
authors.forename: B
authors.initials: B
authors.lastname: Benigno
authors.affiliation: Stanford Women's Cancer Center, Stanford, CA USA.
authors.forename: J
authors.initials: J
authors.lastname: Berek
authors.affiliation: Marin Cancer Care, Greenbrae, CA USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Scripps Cancer Center, San Diego, CA USA.
authors.forename: J
authors.initials: J
authors.lastname: Mason
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Vic Australia.
authors.forename: L
authors.initials: L
authors.lastname: Mileshkin
authors.affiliation: Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Vic Australia.
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: New York Downtown Hospital, New York, NY USA.
authors.forename: M
authors.initials: M
authors.lastname: Moradi
authors.affiliation: South Florida Center for Gynecologic Oncology, Boca Raton, FL USA.
authors.forename: F O
authors.initials: FO
authors.lastname: Recio
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Michener
authors.affiliation: Duke Cancer Institute, Duke University Health System, Durham, NC USA.
authors.forename: A Alvarez
authors.initials: AA
authors.lastname: Secord
authors.affiliation: Morristown Medical Center, Morristown, NJ USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Tchabo
authors.affiliation: University of California, San Francisco & Sutter Health Research Institute, San Francisco, CA USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Chan
authors.affiliation: Medical University of South Carolina, Charleston, SC USA.
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.affiliation: Stanford University Cancer Institute, Stanford, CA USA.
authors.forename: H
authors.initials: H
authors.lastname: Kohrt
authors.affiliation: Prima BioMed, Sydney, NSW Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Gargosky
authors.affiliation: Greenslopes Private Hospital, Royal Brisbane & Women's Hospital, University of Queensland & Gallipoli Research Foundation, Greenslopes, QLD Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Goh
keywords: Dendritic cells; Immunotherapy; Maintenance; Mucin 1; Ovarian cancer