Randomized phase 2 trial of personal dendritic cell (DC)-autologous tumor antigen (ATA) vaccines in newly diagnosed advanced ovary cancer

5560 Background: Advanced ovarian cancer has a high recurrence rate and poor overall survival (OS). The addition of DC-ATA AV-OVA-1, a personal vaccine consisting of autologous DC pulsed with ATA, was investigated to pursue improving OS. Methods: A multi-center, 2:1 double-blind randomized phase 2 trial was designed for patients with newly diagnosed stage 3 or 4 epithelial ovary cancer to determine feasibility of manufacturing study product, and to compare safety and efficacy between DC-ATA and autologous monocytes (MC). Primary endpoint was OS from randomization. Following completion of debulking surgery and chemotherapy, about 6 to 7 months after initial tumor collection, patients were screened and eligible for randomization if a short-term cell line was established from resected tumor, sufficient numbers of MC were collected by leukapheresis, and ECOG status was 0 or 1. Intent was to enroll 99 patients stratified by whether they had residual cancer. MC were differentiated into DC by incubating with IL-4 and GM-CSF. DC-ATA was produced by incubating DC with an ATA lysate prepared from irradiated self-renewing tumor cells. Just prior to each treatment, DC-ATA or MC was admixed in 500 mg GM-CSF and injected s.c. at weeks 1, 2, 3, 8, 12, 16, 20 and 24 (up to 8 doses). Interferon-gamma elispot assays were performed on cryopreserved mononuclear cells obtained from heparinized blood collected prior to each of the first 3 injections. Patients were monitored for adverse events (AE), immune response, OS, and progression-free survival (PFS). Analysis was planned after 44 deaths. Results: During the SARS-CoV-2 pandemic the sponsor terminated accrual and long-term follow up. 70/72 tumors yielded a successful cell line. 20/70 patients did not proceed with leukapheresis. Sufficient MC were collected from 47/50 patients. 45 patients were randomized: 29 to DC-ATA, 16 to MC. Study arms did not differ in patient age, cancer stage, use of neoadjuvant therapy, ECOG status, or residual cancer. Injections were well-tolerated. No patient stopped therapy because of toxicity. Mean number of injections were 7.7 and 7.3. Study arms did not differ in type, proportion or severity of AE, which typically were mild to moderate, short-lived, and self-limited. Number of interferon-gamma elispots were unchanged after MC (p=0.256), but more than doubled after DC-ATA (p-0.0012). The 45 patients were followed for 1 to 31 months from randomization. Median PFS (24 events) was 16.9 months (95% CI 9.2 to 18.7); median OS was not reached (8 deaths). 1-yr OS was 91% (95% CI 78.9, 96.9), 2-yr was 80% (95% CI (49.7, 93.7). There was no difference between study arms in PFS (p=0.837) or OS (p=0.790). Conclusions: Manufacturing DC-ATA was feasible and treatment well-tolerated. There were no differences in AE, PFS or OS between study arms, but survival analyses were severely underpowered. An enhanced immune response was detected after DC-ATA. Clinical trial information: NCT02033616 .