A phase Ib study to assess the safety of the human papillomavirus DNA vaccine (AMV002) in combination with durvalumab for HPV-associated oropharyngeal squamous cell carcinoma

Rahul Ladwa; Janin Chandra; Wai-Ping Woo; Neil Finlayson; Howard Liu; Margaret McGrath; Adrienne See; Brett G Hughes; Caroline L Cooper; Jim E Jackson; Marcin Dzienis; Yan Xu; Benedict Panizza; Ian Frazer; Sandro V Porceddu

doi:10.3389/fonc.2024.1419258

A phase Ib study to assess the safety of the human papillomavirus DNA vaccine (AMV002) in combination with durvalumab for HPV-associated oropharyngeal squamous cell carcinoma

Front Oncol. 2024 Jul 5:14:1419258. doi: 10.3389/fonc.2024.1419258. eCollection 2024.

Authors

Rahul Ladwa^{1

2}, Janin Chandra², Wai-Ping Woo^{2

3}, Neil Finlayson³, Howard Liu^{1

2}, Margaret McGrath¹, Adrienne See¹, Brett G Hughes^{2

4}, Caroline L Cooper^{2

5}, Jim E Jackson⁶, Marcin Dzienis⁶, Yan Xu^{2

3}, Benedict Panizza^{2

7}, Ian Frazer^{2

3}, Sandro V Porceddu^{1

2}

Affiliations

¹ Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.
² Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
³ Jingang Medicine (Australia) Pty Ltd, Brisbane, Australia.
⁴ Department of Cancer Services, Royal Brisbane Hospital, Brisbane, Australia.
⁵ Pathology Queensland, Princess Alexandra Hospital, Brisbane, Australia.
⁶ Department of Cancer Services, Gold Coast University Hospital, Gold Coast, Australia.
⁷ ENT Department, Princess Alexandra Hospital, Brisbane, Australia.

Abstract

Background: Programmed cell death ligand 1 (PD-L1) inhibitors have limited efficacy as monotherapy in patients with recurrent/metastatic (R/M) Human Papilloma Virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). A phase I study of the therapeutic HPV-16 DNA vaccine AMV002 in curatively treated patients with OPSCC demonstrated a measurable immune response against HPV while being associated with high safety and tolerability. This prospective phase Ib single centre pilot study aims to test the safety and tolerability of combined PD-L1 inhibitor, Durvalumab, with AMV002 in 12 patients with recurrent OPSCC.

Methods: Participants had evidence of R/M HPV-associated OPSCC. They received three intradermal administrations of AMV002 with Durvalumab followed by Durvalumab maintenance. Safety and tolerability data was the primary endpoint. The study was conducted with ethical approval (HREC/2018/QMS/47293) in Brisbane, Australia.

Findings: The most common adverse event (AE) related to vaccine administration was erythema at the injection site. There were no grade 3 or 4 vaccine related AEs. There was one presumed immune-related grade 3 elevation in lipase secondary to Durvalumab with no intervention required. No patient ceased study due to treatment-related AEs. At week 16, objective response rate was 8% (N=1) and disease control rate was 17% (N=2). At a median follow up of 25.6 (20.0-26.6) months there was one long term complete response while all other participants developed progressive disease. Of the 11 evaluated patients, 9, (82%) had E6 and/or E7-specific T cell responses to the vaccine.

Conclusion: The combination of AMV002 therapeutic HPV-16 vaccine and Durvalumab was found to be safe and well tolerated with no increased safety signals generated. T cell responses to vaccine were observed but further work will be required to improve efficacy.

Keywords: HPV - human papillomavirus; HPV vaccination; immune checkpoint inhibitor; immunotherapies; oropharangeal cancer.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was in part funded by Metro South Health Research Support Scheme, a Translational Research Institute Drive grant, with in kind support from Admedus Vaccines Pty Ltd and Jingang Medicine (Australia) Pty Ltd. Assay development and the vaccine technologies used in this study was in part supported by Queensland Government development grants, and by funding from the National Health and Medical Research Council of Australia. IHF holds an NHMRC L3 Investigator Grant and is supported by the Merchant Foundation. JC holds a Mid-Career Fellowship from the Garnett Passe Rodney Williams Memorial foundation, with support from the Zelman Cowan Academic Initiatives. We would also like to acknowledge Graham and Trish Bell and the Princess Alexandra Research Foundation for their support. Durvalumab drug was supplied by Astra Zeneca. Jingang Medicine (Australia) Pty Ltd and Astra Zeneca were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.