Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • David Cibula - , Charles University Prague (Author)
  • Lukas Rob - , Charles University Prague (Author)
  • Peter Mallmann - , University of Cologne (Author)
  • Pawel Knapp - , Medical University of Białystok (Author)
  • Jaroslav Klat - , University of Ostrava (Author)
  • Josef Chovanec - , Masaryk Memorial Cancer Institute (Author)
  • Lubos Minar - , Masaryk University (Author)
  • Bohuslav Melichar - , Palacký University Olomouc (Author)
  • Alexander Hein - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Dariusz Kieszko - , Oncological Center of the Lublin Region (Author)
  • Marek Pluta - , Charles University Prague (Author)
  • Jiri Spacek - , Charles University Prague (Author)
  • Pavel Bartos - , Nemocnice AGEL Nový Jičín, a. s. (Author)
  • Pauline Wimberger - , Department of Gynecology and Obstetrics (Author)
  • Radoslaw Madry - , University of Medical Sciences Poznan (Author)
  • Janina Markowska - , University of Medical Sciences Poznan (Author)
  • Joanna Streb - , Jagiellonian University in Kraków (Author)
  • Petr Valha - , Hospital Ceske Budejovice (Author)
  • Hariz Iskandar Bin Hassan - , SOTIO a.s. (Author)
  • Ladislav Pecen - , Czech Academy of Sciences (Author)
  • Lorenzo Galluzzi - , Cornell University (Author)
  • Jitka Fucikova - , SOTIO a.s. (Author)
  • Tereza Hrnciarova - , Charles University Prague (Author)
  • Marek Hraska - , SOTIO a.s. (Author)
  • Jirina Bartunkova - , SOTIO a.s. (Author)
  • Radek Spisek - , SOTIO a.s. (Author)

Abstract

Objective: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. Methods: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3–6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). Results: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42–1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20–0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. Conclusions: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Details

Original languageEnglish
Pages (from-to)652-660
Number of pages9
JournalGynecologic oncology
Volume162
Issue number3
Publication statusPublished - Sept 2021
Peer-reviewedYes

External IDs

PubMed 34294416

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Dendritic-cell based immunotherapy, Immunogenic cell death, Ovarian cancer