Therapeutic HPV vaccine trial +/- anti-CD40 in HPV-driven squamous cell carcinoma

ISRCTN ISRCTN51789191
DOI https://doi.org/10.1186/ISRCTN51789191
ClinicalTrials.gov (NCT) NCT03418480
Clinical Trials Information System (CTIS) 2014-002061-30
Protocol serial number 30900
Sponsor University Hospital Southampton NHS Foundation Trust
Funder European Commission
Submission date
02/11/2016
Registration date
15/12/2016
Last edited
27/01/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-a-vaccine-for-cancers-who-tested-positive-to-the-human-papilloma-virus-hare-40

Contact information

Miss Izabela Eberhart
Public

Southampton Clinical Trials Unit
Southampton General Hospital
MP131
Tremona Road
Southampton
SO16 6YD
United Kingdom

+44 23 8120 3522
HARE-40@soton.ac.uk

Study information

Primary study designInterventional
Study designNon-randomized interventional study
Secondary study designNon randomised study
Study type Participant information sheet
Scientific titleTherapeutic HPV vaccine (BNT113) trial in HPV16 driven carcinoma
Study acronymHARE-40
Study objectivesThe overall aim of this study is to establish a safe and tolerable dose of HPV mRNA vaccine and assess if there is evidence of clinical effect according to irRECIST 1.1.
Ethics approval(s)Approved 18/07/2016, London - West London & GTAC Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8098; westlondon.rec@hra.nhs.uk), ref: 16/LO/0567
Health condition(s) or problem(s) studiedHPV-driven squamous cell carcinoma
Intervention-
Intervention typeBiological/Vaccine
PhaseNot Applicable
Drug / device / biological / vaccine name(s)BNT113
Primary outcome measure(s)

Arm 1A:
The suitable dose of HPV mRNA vaccine is based on defined criteria for DLTs (dose limiting toxicities). This is measured by evaluation of DLTs until 28 days after last study treatment.

Arm 1B:
Disease control rate, defined as the rate of complete response, partial response or stable disease, is measured according to irRECIST 1.1 at the end of treatment CT scan at Day 85.

Key secondary outcome measure(s)

Arm 1A:
1. Adverse event rate is measured according to CTCAE v4.03 at the end of the trial until 28 days after last study treatment
2. Systemic levels of induced HPV-16 specific T-cell and B-cell immune responses are measured using specific biomarker tests at the end of study treatment
3. Duration of detectable vaccine-induced immune response is measured using specifically designed immune-assays at the end of study treatment
4. The clinical and immunological evaluation of DTH sites is assessed prior to vaccination and after the vaccination course, by clinical assessment and tissue biopsy, 48 hours post DTH injection

Arm 1B:
1. Adverse event rate is measured according to CTCAE v4.03 at the end of the trial until 28 days after last study treatment
2. Systemic levels of induced HPV-16 specific T-cell and B-cell immune responses are measured using specific biomarker tests during the course of trial at the end of study treatment
3. Duration of detectable vaccine-induced immune response is measured using specifically designed immune-assays, such as PBMCs during the course of the trial at the end of study treatment
4. The clinical and immunological evaluation of DTH sites is assessed prior to vaccination and after the vaccination course, by clinical assessment and tissue biopsy 48 hours post DTH injection
5. Percentage change in densities of immune cells in tumour tissue (where paired samples can be collected) is assessed using tumour tissue biopsies at baseline and follow-up (Day 85)
6. Numbers of immune cells is assessed by immunohistochemistry or flow cytometry at baseline and follow-up (Day 85)
7. Clinical response is measured according to irRECIST 1.1 at 85 days and 6 and 9 months
8. Disease control rate is measured according to irRECIST 1.1 at 6 and 9 months
9. Best overall response is measured according to irRECIST 1.1 at 9 months
10. Intra-tumoural levels of HPV16‐specific immune responses (where paired tumour samples can be collected) is measured using tumour tissue biopsies at baseline and follow-up (Day 85)
11. Safety/tolerability of HPV mRNA vaccine in terms of the adverse event rate is measured according to CTCAE v4.03 at 36 and 85 days
12. Grade 3 or above vaccine- or combination administration-related toxicity is measured within 90 days after the last administration of study drugs
13. Progression-Free Survival (PFS) is measured from baseline to date of disease progression or death, from any cause
14. Overall Survival (OS) is measured from baseline to date of disease progression or death, from any cause
15. Disease Specific Interval (DSI) is measured from baseline to date of disease progression or death, from any cause

Completion date24/01/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration153
Total final enrolment15
Key inclusion criteriaInclusion Criteria Arm 1A:
1. Previous HPV16+ head and neck squamous cell carcinoma
2. At least 12 months after completion of treatment
3. Within 5 years of treatment completion
4. Currently no clinical evidence of disease
5. ECOG performance status 0 or 1
6. Able to provide written informed consent

Inclusion Criteria Arm 1B:
1. HPV16+ head and neck, cervical, anogenital and penile carcinoma patients with recurrent disease.
2. Intention to treat is palliative.
3. Patient willing to have repeated tumour biopsies and re-biopsy deemed safe and feasible clinically.
4. Tissue samples available confirming HPV16+ disease to send to Central Laboratory.
Key exclusion criteria1. Patients unable to consent
2. Under 18 years of age
3. Systemic steroids or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry. Replacement steroids for adrenal insufficiency/failure are allowed.
4. Major surgery in the preceding three to four weeks, which the patient has not yet recovered from
5. Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection
6. Patients with any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease
7. Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study
8. Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing
9. Patients who have a positive pregnancy test
10. Fertile males or females who are unable or unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, intrauterine device, or intrauterine hormone-releasing system) during study treatment and until end of treatment +28 days (day 113)
11. Elevated Liver Function Tests – ALT, AST, Bilirubin
12. Any other investigational drug within 28 days or 5 half-lives depending on what gives the longer range before the first treatment of this study
Date of first enrolment01/01/2017
Date of final enrolment19/07/2023

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centres

University Hospital Southampton
Southampton University Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
The Christie NHS Foundation Trust
550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
IPD sharing planThe current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Study website Study website 11/11/2025 11/11/2025 No Yes

Editorial Notes

27/01/2025: The following changes were made:
1. The study type prevention was replaced by treatment.
2. The intention to publish date was changed from 24/01/2025 to 31/10/2025.
3. The publication and dissemination plan was updated.
02/02/2024: The following changes were made to the study record:
1. Ethics approval details added.
2. The overall study end date was changed from 31/07/2024 to 24/01/2024.
3. The intention to publish date was changed from 30/07/2025 to 24/01/2025.
05/09/2023: The recruitment end date was changed from 31/12/2023 to 19/07/2023.
17/04/2023: The following changes have been made:
1. The scientific title has been changed from "Therapeutic HPV vaccine trial +/- anti-CD40 in HPV-driven squamous cell carcinoma" to "Therapeutic HPV vaccine (BNT113) trial in HPV16-driven carcinoma".
2. The intervention name has been added.
3. The final enrolment number has been added.
4. The recruitment end date has been changed from 31/12/2022 to 31/12/2023.
5. University Hospital Southampton and The Christie NHS Foundation Trust have been added to the trial participating centres and Southampton Clinical Trials Unit removed .
17/03/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2022 to 31/12/2022.
2. The overall trial end date has been changed from 31/01/2023 to 31/07/2024.
3. The intention to publish date has been changed from 31/01/2024 to 30/07/2025.
4. The trial website has been added.
5. The study contact has been updated.
07/04/2020: The recruitment end date was changed from 31/01/2021 to 31/03/2022.
04/07/2019: ClinicalTrials.gov number added.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Gynae; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs, Cancer/ Malignant neoplasms of male genital organs, Cancer/ Malignant neoplasms of ill-defined, secondary and unspecified sites" to "HPV-driven squamous cell carcinoma" following a request from the NIHR.
07/02/2019: The following changes were made:
1. The recruitment end date was changed from 31/01/2019 to 31/01/2021.
2. The overall trial end date was changed from 31/01/2021 to 31/01/2023.
3. Thee intention to publish date was changed from 31/01/2022 to 31/01/2024.
22/01/2018: The recruitment end date was changed from 01/01/2018 to 31/01/2019.
11/08/2017: Cancer Help UK lay summary link added.
06/06/2017: Internal review

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