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

Cancer Gene Therapy volume 29, pages 369–382 (2022)Cite this article

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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.

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Fig. 1: Consort diagram.
Fig. 2: Treatment-related adverse events.
Fig. 3: Efficacy analysis from time of study randomization.

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Acknowledgements

The authors would like to thank Brenda Marr for her help in manuscript preparation and submission.

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Authors and Affiliations

  1. University of South Alabama - Mitchell Cancer Institute, Mobile, AL, USA

    Rodney P. Rocconi

  2. Billings Clinic, Billings, MT, USA

    Erin E. Stevens & Justin N. Bottsford-Miller

  3. Augusta University, Augusta, GA, USA

    Sharad A. Ghamande

  4. Greenville Health System, Greenville, SC, USA

    Jeffrey Elder

  5. Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Leslie L. DeMars

  6. Josephine Ford Cancer Institute, Detroit, MI, USA

    Adnan Munkarah

  7. Gradalis, Inc., Dallas, TX, USA

    Phylicia Aaron, Laura Stanbery, Gladice Wallraven, Ernest Bognar, Meghan Manley, Staci Horvath, Luisa Manning & John Nemunaitis

  8. ProMedica, Toledo, OH, USA

    Adam Walter

  9. Mayo Clinic, Rochester, MN, USA

    Evanthia Galanis

  10. University of Cincinnati Cancer Center, Cincinnati, OH, USA

    Thomas Herzog

  11. Arizona Oncology, Phoenix, AZ, USA

    Bradley J. Monk

  12. MD Anderson Cancer Center, Houston, TX, USA

    Robert L. Coleman

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Correspondence to John Nemunaitis.

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Rocconi, R.P., Stevens, E.E., Bottsford-Miller, J.N. et al. Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. Cancer Gene Ther 29, 369–382 (2022). https://doi.org/10.1038/s41417-021-00317-5

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