A phase I combination study of vigil and atezolizumab in recurrent/refractory advanced-stage ovarian cancer: Efficacy assessment in BRCA1/2-wt patients.
3002 Background: Recent studies have shown poor clinical outcomes and limited survival advantage to checkpoint inhibitors (CIs) in advanced stage ovarian cancer (OvC). Vigil is a personalized precision vaccine constructed from autologous tumor tissue transfected with a DNA plasmid encoding GM-CSF and bi-shRNA-furin thereby creating TGFβ expression control and enhancing immune activation. Phase 1 and 2 trials in OvC demonstrate safety, functional immune activation and clinical response benefit. Combining Vigil with CIs may broaden responsiveness of immunotherapy in OvC. Methods: This is a randomized, 3-part safety Phase 1 study of Vigil in combination with Atezolizumab in recurrent OvC patients. Part 2 is a randomized, intra-patient crossover study of Vigil first (VF) or Atezolizumab first (AF) for two cycles followed by sequence of the combination of the two agents. Vigil (1 x 106 or 1 x 107 cells/ml) or Atezolizumab (1200mg) were administered 1x every 21 days each cycle until progression or untoward adverse event. We now report the preliminary results of part 2 of the study. Results: Twenty-one patients were randomized (1:1) to VF (n = 11) or AF (n = 10), groups were similar in demographics. Grade 3/4 toxic events occurred in 17% of AF patients compared to 3% in VF patients. Median OS of VF patients (n = 11) was not reached vs. AF (n = 10) 10.8 months suggested modest advantage to VF (HR 0.33, one-sided p 0.097). However, the subset analysis of BRCA1/2 wild type (wt) demonstrated more significant overall survival benefit in VF (n = 7) median OS not reached vs. AF (n = 7) 5.2 months (HR 0.12, one-sided p 0.015). Conclusions: The combination of Vigil immunotherapy and checkpoint inhibitor atezolizumab in recurrent OvC demonstrated safety and suggest a lower toxicity profile and a significant OS advantage in recurrent BRCA1/2-wt OvC patients treated with Vigil first followed by the combination of Vigil and Atezolizumab. Clinical trial information: NCT03073525 . [Table: see text]