Phase 1 Clinical Trial of FluBHPVE6E7 Immunotherapy for HPV16-Associated Oropharyngeal Cancer

Official title

A Phase 1 Study of FluBHPVE6E7 Immunotherapy in Patients With HPV16- Associated Oropharyngeal Squamous Cell Carcinoma

Overview

A clinical study of an immunotherapy in patients with head or neck cancers associated with the HPV16 virus

Detailed description

Squamous cell carcinomas of the head and neck (HNSCC) rank as the sixth most common cancer globally, with approximately 575,000 new cases diagnosed each year. In recent years, there has been a rising incidence in younger patients who have limited exposure to traditional risk factors such as smoking and alcohol. This increase is closely associated with HPV infection, particularly HPV-16, which is strongly linked to oropharyngeal cancer. Treatment for HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is highly individualized, depending on the disease stage, patient comorbidities, and personal preferences. In this phase 1 study, patients with HPV-16-associated OPSCC are being treated with the immunotherapeutic delNS-vector expressing the HPV-16 oncogenes E6 and E7, administered both intratumorally and intramuscularly.

Interventions

• Biological FluBHPVE6E7
  Intratumoral administration for first dose followed by intramuscular administration for subsequent doses at recommended dose level and determined schedule.

Primary outcome measures

• Frequency and severity of adverse events (AEs) [Time frame: 7 days]

Secondary outcome measures (9)

• Intralesional T-cell infiltration [Time frame: 24 weeks]
• Biodistribution [Time frame: 24 weeks]
• Virus recovery in oropharyngeal secretion samples [Time frame: 7 days]
• Virus recovery in saliva [Time frame: 7 days]
• Frequency and severity of adverse events (AEs) [Time frame: 24 weeks]
• Disease-free survival (DFS) [Time frame: 60 months]
• Overall survival (OS) [Time frame: 60 months]
• Induction of HPV-specific T-cell response following FluBHPVE6E7 administration [Time frame: 24 weeks]
• Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration [Time frame: 24 weeks]

Eligibility criteria

Inclusion criteria

• Female or male patients, 18-65 years of age, with newly diagnosed, histologically confirmed p16- and HPV16-positive oropharyngeal squamous cell carcinoma with locoregional advanced disease including the following stages:

• T2N2-3, M0
• T3N0-3, M0
• T4N0-3, M0
• Primary tumour accessible for biopsy and intratumoural administration
• No evidence of distant metastatic disease (HPV16-positive secondary tumours are permissible)
• Karnofsky 100 - 70 (ECOG 0 or 1)
• Life expectancy of at least 6 months
• Normal screening ECG or screening ECG with no clinically significant findings requiring immediate treatment, as judged by the investigator
• Women of childbearing potential: Negative serum pregnancy test at screening
• Agree to use a reliable form of contraception until the end of the study treatment period.
• Provides written informed consent

Exclusion criteria

• Distant metastases
• Secondary, not HPV16-associated, malignancy
• History of malignancy other than the target malignancy to be investigated in this trial unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Clinically significant out of range haematological, renal or hepatic laboratory tests which cannot be explained by the underlying disease
• Any vaccination within 1 week before day 0
• Active significant viral infections including influenza, CMV, and EBV within 4 weeks before receiving study treatment
• Co-infection with hepatitis B, hepatitis C, or HIV or having other immune deficient states
• Influenza-like illness (ILI) within 4 weeks before day 0
• Known hypersensitivity to Tamiflu or any of its components
• Pregnancy, breastfeeding
• Serious, concomitant disorder, including active systemic infection requiring treatment
• Proven or suspected systemic lupus erythematosus, thyroiditis, inflammatory bowel disease including Crohn's disease or multiple sclerosis
• Immunosuppression including any concurrent condition requiring the continued use of systemic steroids, or the use of immunosuppressive agents, disease modifying doses of anti-rheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate), and biologic disease modifying drugs such as TNF-α inhibitors (e.g. infliximab, adalimumab or etanercept). Corticosteroids must be discontinued \> 4 weeks prior to day 0 of study medication administration. Eye drops or ear drops containing corticosteroids are permissible.
• Prior major surgery within 4 weeks before day 0
• Any current significant cardiac, hepatic or renal disease or history of clinically significant, medically unstable disease (e.g. chronic renal failure; angina, myocardial ischemia or infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias)
• Participation in another experimental protocol/use of investigational drug within two months before day 0
• Any condition that, in the judgment of the investigator, might prevent safe participation in the study or interfere with study objectives
• Unability to comply with the protocol requirements

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 1 center

• Medical University Vienna — Vienna

Identifiers

NCT: NCT06589609 · BS-03 · 2024-514413-36-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗