BACKGROUND: Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer. PATIENTS AND METHODS: This multicenter, single-arm, phase 2a study (NCT04405349, registered 26 May 2020) enrolled adult patients with persistent, r/m HPV16-positive cervical cancer. Patients received 3 mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200 mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment. RESULTS: Between June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95% CI 2.2 to n.r.), median progression-free survival was 4.1 months (95% CI 2.1 to 6.2), and median overall survival was 21.3 months (95% CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22/36 (61%). CONCLUSIONS: The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r/m HPV16-positive cervical cancer, especially if PD-L1-positive.

Center hospital de l'Ardenne Libramont Belgium

Department of gynecological oncology Oslo University Hospital Oslo Norway

Department of Gynecology and Obstetrics Hannover Medical School Hannover Germany

Department of Gynecology and Obstetrics Medical Faculty Dresden Germany

Department of Gynecology and Obstetrics Technische Universität Dresden Dresden Germany

Department of Gynecology and Obstetrics University Hospital Mannheim Mannheim Germany

Department of Gynecology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Obstetrics and Gynecology Bulovka University Hospital Na Bulovce Budinova 67 2 Prague Czech Republic

Gynecologic Oncology Department Maria Sklodowska Curie National Research Institute of Oncology in Warsaw Krakow Branch Krakow Poland

Gynecologic Oncology Department Maria Sklodowska Curie National Research Institute of Oncology Warzawa Poland

Gynecology and Obstetrics Faculty of Medicine University of Augsburg Augsburg Germany

Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Masaryk Memorial Cancer Institute Brno Czech Republic

Medical Oncology University Hospital Ghent Gent Flanders Belgium

Nykode Therapeutics ASA Oslo Oslo Norway

University Clinic Saint Luc Bruxelles Belgium

University Hospital Kralovske Vinohrady Praha Czech Republic

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