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

Autor: Rocconi RP; University of South Alabama - Mitchell Cancer Institute, Mobile, AL, USA., Stevens EE; Billings Clinic, Billings, MT, USA., Bottsford-Miller JN; Billings Clinic, Billings, MT, USA., Ghamande SA; Augusta University, Augusta, GA, USA., Elder J; Greenville Health System, Greenville, SC, USA., DeMars LL; Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA., Munkarah A; Josephine Ford Cancer Institute, Detroit, MI, USA., Aaron P; Gradalis, Inc., Dallas, TX, USA., Stanbery L; Gradalis, Inc., Dallas, TX, USA., Wallraven G; Gradalis, Inc., Dallas, TX, USA., Bognar E; Gradalis, Inc., Dallas, TX, USA., Manley M; Gradalis, Inc., Dallas, TX, USA., Horvath S; Gradalis, Inc., Dallas, TX, USA., Manning L; Gradalis, Inc., Dallas, TX, USA., Walter A; ProMedica, Toledo, OH, USA., Galanis E; Mayo Clinic, Rochester, MN, USA., Herzog T; University of Cincinnati Cancer Center, Cincinnati, OH, USA., Monk BJ; Arizona Oncology, Phoenix, AZ, USA., Coleman RL; MD Anderson Cancer Center, Houston, TX, USA., Nemunaitis J; Gradalis, Inc., Dallas, TX, USA. jnemunaitis@gradalisinc.com.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2022 Mar; Vol. 29 (3-4), pp. 369-382. Date of Electronic Publication: 2021 Mar 22.
DOI: 10.1038/s41417-021-00317-5
Abstrakt: 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 BRCA wt 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 BRCA wt patients.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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