Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer

Rodney P. Rocconi, Erin E. Stevens, Justin N. Bottsford-Miller, Sharad A. Ghamande, Jeffrey Elder, Leslie L. DeMars, Adnan Munkarah, Phylicia Aaron, Laura Stanbery, Gladice Wallraven, Ernest Bognar, Meghan Manley, Staci Horvath, Luisa Manning, Adam Walter, Evanthia Galanis, Thomas Herzog, Bradley J. Monk, Robert L. Coleman, John Nemunaitis

Research output: Contribution to journalArticlepeer-review

Abstract

Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFβ expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCAwt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCAwt patients.

Original languageEnglish (US)
JournalCancer Gene Therapy
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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