Front-line Vigil Immunotherapy Well Tolerated in Patients with BRCA1, BRCA2 Wild Type Mutations

Front-line use of vigil immunotherapy as maintenance in the treatment of stage 3-4 ovarian cancer was well tolerated as demonstrated a relapse-free survival (RFS) clinical benefit, particularly in patients with BRCA1 and BRCA2 wildtype (wt) mutations, according to a study from the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer.

Despite advances, overall prognosis for advanced epithelial ovarian cancer (EOC) remains poor. Considering elevated TGFβ expression correlates with poor prognosis in ovarian cancer, the researchers aimed to determine whether a maintenance vigil could provide improvement in RFS.

Vigil is an autologous tumor cell vaccine constructed from autologous harvested tumor tissue transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin, thereby creating TGFβ expression control.

Researchers performed a randomized double-blind placebo-controlled trial of vigil versus placebo in patients with advanced front-line ovarian cancer. The RFS, the safety, and the proportion of recurrences were endpoints. Patients who achieved complete clinical response were randomized after completion of front-line surgery and chemotherapy. All patients received 1 × 10e7 cells/ml of vigil or placebo intradermally once per month for up to 12 doses.

The study randomized 91 patients, with 62 patients tested for BRCA1 and BRCA2 status. The vigil group showed no added overall toxicity compared with the control group. No grade 4-5 toxicities were observed; however, grade 2-3 toxic events were observed in 18% of the control group patients (common bone pain, fatigue) compared with 8% of the vigil group patients (common nausea, musculoskeletal pain).

From the time of randomization, median RFS for all 91 patients was favorable in the vigil group. Stratified by BRCA status, an advantage in RFS was seen in the BRCA1 and BRCA2wt patients in the vigil group compared with the control group from the time of randomization and HR of 0.49 from time of surgery. The median time from surgery to randomization was 208.5 days in the vigil group versus 200 days in the control group. Of the patients with BRCA1 and BRCA2wt who were treated with vigil, 62.5% were relapse-free compared with 29% of patients in the placebo cohort at the time of analysis.

The study found that front-line use of vigil immunotherapy as maintenance in stage III—IV ovarian cancer was well tolerated and showed trend in RFS clinical benefit. Additionally, BRCA1 and BRCA2wt disease showed statistically significant benefits, according to the study authors.

Reference

1. Randomized double-blind placebo controlled trial of primary maintenance vigil immunotherapy (VITAL study) in stage III/IV ovarian cancer: Efficacy assessment in BRCA1/2-wt patients. SGO conference abstract. Published March 30, 2020. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/17080. Accessed April 2, 20