Cvac as Maintenance Treatment in Patients With Epithelial Ovarian Cancer in Complete Remission Following First-line Chemotherapy or Second-line Treatment

This study proposes a nontoxic immunotherapeutic approach to extend overall survival in patients in complete remission. Most patients with ovarian cancer achieve complete clinical remission after optimal debulking surgery and first-line platinum-based chemotherapy. However, most patients, despite high response rates to first-line treatment, will relapse and undergo subsequent chemotherapy. Generally, the progression-free interval between treatments becomes shorter with each relapse, and the patient eventually dies of the disease. For production of Cvac, each patient's cells were enriched using cell separation techniques. The patient's cells were cultured for 5 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in AIM V® serum-free tissue culture medium (Thermo Fisher Scientific) to cultivate the growth of dendritic cells (DC). The culture was pulsed overnight with the antigen (mannosylated mucin 1 fusion protein \[M-FP\]) to arm the DCs to the specific mucin 1 antigen. After harvesting, the M-FP-pulsed DCs were formulated as a finished product (Cvac) in 1 mL aliquots, diluted in 5% human serum albumin (HSA) and 10% dimethyl sulfoxide (DMSO) at an approximate concentration of 60 × 10\^6 viable DCs/mL. The vials were cryopreserved and stored in the vapor phase of liquid nitrogen at the manufacturing facility. Different participants were enrolled in the 2 parts of the study. Part A To be eligible for participation, patients were diagnosed with stage III or IV epithelial ovarian cancer, underwent optimal debulking surgery (≤ 1 cm of residual disease), underwent platinum and taxane chemotherapy, with or without bevacizumab, and had a tumor that overexpressed mucin 1, as well as met all other study inclusion and exclusion criteria at screening. Patients who met all study inclusion and exclusion criteria were randomized in a 1:1 double-blinded fashion to either the Cvac (active) group or the placebo (control) group. After randomization, patients underwent mononuclear cell (MNC) collection for production of the study agent and then began first-line chemotherapy. After completion of chemotherapy and confirmation of complete clinical and radiological remission (Baseline), patients were entered into the treatment phase of the study. A total of 76 patients were recruited and randomized at centers in Europe, North America, and Australia. Part B To be eligible for participation, patients had first-line platinum-based chemotherapy with a complete response lasting for at least 6 months prior to relapse and achieved second remission following standard platinum-based second-line chemotherapy with or without a second bulk-reducing surgery, and had a tumor that over-expressed mucin 1, as well as met all other study inclusion and exclusion criteria. Patients who met all study inclusion and exclusion criteria were randomized in a 1:1 fashion to either the Cvac (active) group or the observational standard of care (control) group. After randomization, only patients randomized to Cvac underwent MNC collection for production of the study agent. After confirmation of no evidence of disease at the Baseline visit, patients were entered into the treatment phase of the study. A total of 15 patients were recruited and randomized at centers in Europe.