HARE-40: HPV Anti-CD40 RNA vaccinE (HARE-40)

Therapeutic HPV Vaccine (BNT113) Trial in HPV16 Driven Carcinoma

HARE-40 is a phase I/II vaccine dose escalation study with two different arms: Arm 1A will perform intrapatient dose escalation in patients with previously treated HPV16+ Head & Neck Cancer using two dose cohorts to establish a safe, tolerable and recommended dose of HPV vaccine.

Arm 1B will perform intrapatient dose escalation in patients with advanced HPV16+ cancer (head and neck, anogenital, penile, cervical and other) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.

Study Overview

• Status: Completed
• Conditions: Unknown Primary Tumors; Head and Neck Neoplasm; Cervical Neoplasm; Penile Neoplasms Malignant; Human Papilloma Virus Related Carcinoma
• Intervention / Treatment: Drug: BNT113

Detailed Description

HARE-40 is a phase I/II vaccine dose escalation trial with two arms (Arm 1A and Arm 1B) in which we will test BNT113 as monotherapy. We will undertake a multi-centre phase I, open label trial in patients with previous HPV16+ HNSCC without current clinical evidence of disease (Arm 1A) and in patients with HPV16+ advanced disease (Arm 1B). The HPV16 antigen-specific immune response will be evaluated before and after treatment in circulating blood and, where samples have been collected, in tumour and skin biopsies.

Arms 1A and 1B will escalate BNT113 in each patient (intrapatient dose escalation) up to the specified target dose of the cohort to establish a safe, tolerable and recommended dose of BNT113 in patents who are disease free (Arm 1A) and those with advanced disease (Arm 1B).

Subset of patients in Arm 1B will also be assessed for response to the vaccine in terms of a significant increase of immune cells following BNT113 administration and according to irRECIST1.1 (all 29 patients including the expansion cohort) and other endpoints.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Phase One Clinic; Email: phaseoneclinic@soton.ac.uk

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Univeristy Hospitals Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Arm 1A:

• Previous HPV16+ head and neck squamous cell carcinoma.
• At least 12 months after completion of treatment.
• Within 5 years of treatment completion.
• Currently no clinical evidence of disease.
• ECOG performance status 0 or 1.

Arm 1B:

• HPV16+ head and neck, cervical, anogenital and penile carcinoma patients with recurrent disease.
• Intention to treat is palliative.
• Patient willing to have repeated tumour biopsies and re-biopsy deemed safe and feasible clinically.
• Tissue samples available confirming HPV16+ disease to send to Central Laboratory.

Exclusion Criteria:

• Patients unable to consent.
• Any patient who has been previously vaccinated in any Arm of the trial.
• <18 years
• Systemic steroids (prednisolone >10 mg/day or equivalent) 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.
• Major surgery in the preceding three to four weeks, which the patient has not yet recovered from.
• Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection.
• Patients with clinically relevant autoimmune disease will be excluded.
• Patients who are known to be allergic to any of the excipients or constituents of the vaccine
• 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.
• 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.
• 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.
• Patients who have a positive pregnancy test or who are breast feeding.
• Fertile males or females who are unable or unwilling to use an effective method of birth control (eg. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, intrauterine device, or intrauterine hormone-releasing system) during study treatment and until 28 days after patients finish the study treatment.
• Elevated Liver Function Tests - ALT >3.0 x ULN, AST >3.0 x ULN, Bilirubin >3.0 x ULN.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RNA Vaccine A; Arm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine. - COMPLETE no longer recruiting	Drug: BNT113; Intradermal vaccine
Experimental: RAN Vaccine B; Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine. OPEN to recruitment	Drug: BNT113; Intradermal vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A)	Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA	3 months

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: BioNTech SE
• Investigators: Principal Investigator: Ioannis Karydis, Dr, University Hospitals Southampton NHS Foundation Trust; Study Chair: Christian Ottensmeier, Prof, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2017
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: November 15, 2017
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Neoplasms, Male; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Squamous Cell; Penile Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Genital Diseases, Female; Neoplasms; Uterine Cervical Neoplasms; Head and Neck Neoplasms; Carcinoma; Neoplasms, Unknown Primary; Papilloma; Penile Neoplasms
• Other Study ID Numbers: RHMCAN0983; 2014-002061-30 (EudraCT Number); ISRCTN51789191 (Other Identifier: ISRCTN Reference No.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No