Abstract
ObjectiveDCVAC/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. MethodsIn 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). ResultsBetween 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. ConclusionsDCVAC/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.
Highlights
Cytoreductive surgery followed by platinum and taxane combination is the standard first-line treatment for advanced ovarian cancer [1]
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
Median overall survival (OS) was significantly prolonged in the DCVAC/OvCa group (HR 0.38, 95% confidence intervals (CI) 0.20–0.74, P = 0.003; data maturity 56.3%)
Summary
Cytoreductive surgery followed by platinum and taxane combination is the standard first-line treatment for advanced ovarian cancer [1]. Most patients diagnosed with advanced ovarian cancer suffer from recurrences [2]. In these patients, survival correlates with the duration of remission after the last dose of platinum-based chemotherapy and platinum-based chemotherapy doublet remains the treatment of choice in patients recurring >6 months after first-line treatment [2]. Alternative immunotherapeutic approaches include dendritic cell (DC)-based immunotherapies, such as autologous DCs expanded, activated, and loaded with a source of tumor-associated antigens (TAAs) ex vivo [5]. DCVAC/OvCa was developed as an active, DC-based immunotherapy for ovarian cancer, harnessing allogeneic tumor cells killed by high hydrostatic pressure as a source of multiple TAAs [6,7]. The rationale for loading DCs with a broad range of TAAs, as opposed to a single antigen, is based on the increased likelihood of generating a polyclonal T-cell response against malignant cells, maximizing the potency of immunization and minimizing the probability of immune evasion via antigen loss [8]
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