Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study
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...
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010827.full |
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| author | Hannelore Denys Frederik Marmé Frederic Forget Lukas Rob Pawel Blecharz Kristina Lindemann Peter Hillemanns Linn Wölber Theresa Link Jean-Francois Baurain Mariusz Bidziński Linn Woelber Michal ZikÁN Josef Chovanec Christian Dannecker Stéphanie Henry Hannelore G Denys Velko Minchev Anders Rosholm Kaja C G Berg Roberto S Oliveri Marchela Koleva Bozhil Robev |
| author_facet | Hannelore Denys Frederik Marmé Frederic Forget Lukas Rob Pawel Blecharz Kristina Lindemann Peter Hillemanns Linn Wölber Theresa Link Jean-Francois Baurain Mariusz Bidziński Linn Woelber Michal ZikÁN Josef Chovanec Christian Dannecker Stéphanie Henry Hannelore G Denys Velko Minchev Anders Rosholm Kaja C G Berg Roberto S Oliveri Marchela Koleva Bozhil Robev |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7dcf396309044ed58d8c1af3f681ab60 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-7dcf396309044ed58d8c1af3f681ab602025-01-09T16:30:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010827Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study Hannelore DenysFrederik Marmé0Frederic Forget1Lukas Rob2Pawel Blecharz3Kristina Lindemann4Peter Hillemanns5Linn WölberTheresa Link6Jean-Francois Baurain7Mariusz Bidziński8Linn Woelber9Michal ZikÁN10Josef Chovanec11Christian Dannecker12Stéphanie HenryHannelore G Denys13Velko MinchevAnders Rosholm14Kaja C G Berg15Roberto S Oliveri16Marchela KolevaBozhil RobevDepartment of Gynecology and Obstetrics, University Hospital Mannheim, Mannheim, GermanyCenter hospital de l’Ardenne, Libramont, BelgiumUniversity Hospital Kralovske Vinohrady, Praha, Czech RepublicGynecologic Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw Krakow Branch, Krakow, PolandDepartment of gynecological oncology, Oslo University Hospital, Oslo, NorwayDepartment of Gynecology and Obstetrics, Hannover Medical School, Hannover, GermanyDepartment of Gynecology and Obstetrics, Medical Faculty, Dresden, GermanyUniversity Clinic Saint-Luc, Bruxelles, BelgiumGynecologic Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Warzawa, PolandDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Obstetrics and Gynecology, Bulovka University Hospital Na Bulovce Budinova 67/2, Prague, Czech RepublicMasaryk Memorial Cancer Institute, Brno, Czech RepublicGynecology and Obstetrics, Faculty of Medicine, University of Augsburg, Augsburg, GermanyMedical Oncology, University Hospital Ghent, Gent, Flanders, BelgiumNykode Therapeutics ASA, Oslo, Oslo, NorwayNykode Therapeutics ASA, Oslo, Oslo, NorwayNykode Therapeutics ASA, Oslo, Oslo, NorwayBackground 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.https://jitc.bmj.com/content/13/1/e010827.full |
| spellingShingle | Hannelore Denys Frederik Marmé Frederic Forget Lukas Rob Pawel Blecharz Kristina Lindemann Peter Hillemanns Linn Wölber Theresa Link Jean-Francois Baurain Mariusz Bidziński Linn Woelber Michal ZikÁN Josef Chovanec Christian Dannecker Stéphanie Henry Hannelore G Denys Velko Minchev Anders Rosholm Kaja C G Berg Roberto S Oliveri Marchela Koleva Bozhil Robev Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study Journal for ImmunoTherapy of Cancer |
| title | Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study |
| title_full | Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study |
| title_fullStr | Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study |
| title_full_unstemmed | Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study |
| title_short | Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study |
| title_sort | safety and efficacy of the therapeutic dna based vaccine vb10 16 in combination with atezolizumab in persistent recurrent or metastatic hpv16 positive cervical cancer a multicenter single arm phase 2a study |
| url | https://jitc.bmj.com/content/13/1/e010827.full |
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