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

• Published in: Gynecologic oncology Vol. 162; no. 3; pp. 652 - 660
• Main Authors: Cibula, David, Rob, Lukas, Mallmann, Peter, Knapp, Pawel, Klat, Jaroslav, Chovanec, Josef, Minar, Lubos, Melichar, Bohuslav, Hein, Alexander, Kieszko, Dariusz, Pluta, Marek, Spacek, Jiri, Bartos, Pavel, Wimberger, Pauline, Madry, Radoslaw, Markowska, Janina, Streb, Joanna, Valha, Petr, Hassan, Hariz Iskandar Bin, Pecen, Ladislav, Galluzzi, Lorenzo, Fucikova, Jitka, Hrnciarova, Tereza, Hraska, Marek, Bartunkova, Jirina, Spisek, Radek
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carcinoma, Ovarian Epithelial - therapy; Combined Modality Therapy; Dendritic Cells - immunology; Dendritic Cells - transplantation; Dendritic-cell based immunotherapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; Humans; Immunogenic cell death; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Middle Aged; Neoplasm Staging; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Dendritic-cell based immunotherapy; Immunogenic cell death; Ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2021.07.003

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. 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). 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. 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. •Randomized trial of DCVAC/OvCa, dendritic cell-based immunotherapy in platinum-sensitive ovarian cancer.•The addition of DCVAC/OvCa to second-line chemotherapy had a favorable safety profile.•DCVAC/OvCa did not improve progression-free survival, but did prolong overall survival by 13.4 months.•DVCAC/OvCa plus chemotherapy enhanced surrogate T-cell activity.