HARE-40
Research type
Research Study
Full title
Therapeutic HPV vaccine trial +/- anti-CD40 in HPV-driven squamous cell carcinoma.
IRAS ID
147980
Contact name
Kerry-Ann Lee
Contact email
Sponsor organisation
University Hospital Southampton NHS Foundation Trust
Eudract number
2014-002061-30
Duration of Study in the UK
5 years, 5 months, 29 days
Research summary
Research Summary:
Human papillomaviruses (HPV) causes about 5% of cancer worldwide. High-risk subtypes cause cervical, anogenital and head and neck cancer. Conventional treatments for these cancers include surgery, radiotherapy and chemotherapy: each of these has significant side effects, and new treatment modalities are clearly required.
Immunotherapy offers the option of long term disease control by activating the patient’s own immune system to destroy the cancer. This study aims to combine a vaccine (specific for HPV) and an antibody (to stimulate the patient’s immune system), to generate an immune response against HPV.In stage 1 of this Phase I/IIa trial, the vaccine will initially be given alone in an escalating dose to patients who have been previously treated, are disease free but are at risk of relapse (Arm 1A). The optimal dose will then be used to treat patients with end-stage disease (either head and neck, cervical or anogenital cancer) in Arm 1B.
Lay summary of study results: Who carried out the research?
HARE-40 was coordinated by Southampton Clinical Trials Unit and was sponsored by University Hospital Southampton NHS Foundation Trust. This trial was funded by a European Grant (IACT) with additional financial support from BioNTech SE, the ECMC and SCTU Cancer Research UK core funding.Where and when the study took place?
HARE-40 was conducted from 2017 to 2023 in 2 UK hospitals.Why was the research needed?
Head and neck cancer is the sixth commonest cancer, with poor survival rates. Current treatment (surgery, radiotherapy and/or chemotherapy) can lead to lifelong problems. An increasing number of these cancers are due to human papillomavirus (HPV). Treatments that boost the immune system to fight cancer offer an alternative to current treatments, with fewer side effects. This research studied a vaccine developed by BioNTech (BNT113) designed to target HPV16-driven cancer.What were the main questions studied?
The first aim was to find a safe dose for BNT113. The second aim was to measure the efficacy of BNT113 in terms of cancer disease control.Who participated in the study?
There were two Arms (1A and 1B) in the study. Arm 1A included patients with previous HPV16+ head and neck small cell cancer, disease free at least 12 months after curative treatment (n=17, 76% were male, median age 63). Arm 1B included patients with HPV16+ advanced cancers (including head and neck, anal, cervical) treated palliatively (n=13, 77% were female, median age 58).What treatments or interventions did the participants take/receive?
BNT113 was given intravenously once a week for four weeks, then every two weeks for another four doses, with dose increased from 7.2 μg to 29 μg (Arm 1A cohort 1) or to 72.8 μg (Arm 1A cohort 2 and Arm 1B).What medical problems (adverse reactions) did the participants have?
A total of 19 (63%) people received all 8 doses. Although no dose-limiting toxicities (DLTs) were reported, 2 patients in Arm 1A reached their individual maximum tolerated doses (MTDs). Nausea, fatigue, and headaches were the most commonly reported symptoms. Most symptoms were of low severity. Ten participants (2 in cohort 1A) experienced a serious adverse event.What were the results of the study?
The vaccine was well tolerated, suggesting it could be safely tested in future research. Disease control was seen in 5 out of 7 patients (71%) in Arm 1B with post-treatment tumour scans. The vaccine produced an immune response in both arms.How has this study helped patients and researchers?
BNT113 was generally well tolerated by patients, suggesting that future research could further investigate how well it works. Most patients showed a response in terms of their immune system, as well as control of disease.REC name
London - West London & GTAC Research Ethics Committee
REC reference
16/LO/0567
Date of REC Opinion
18 Jul 2016
REC opinion
Further Information Favourable Opinion