Oropharyngeal Squamous Cell Carcinoma (SCC)
Conditions
Keywords
immunotherapy, Oropharyngal squamous cell carcinoma, HPV-16, Human papilloma virus, cancer, Head and neck cancer
Brief summary
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
BIOLOGICALFluBHPVE6E7
Intratumoral administration for first dose followed by intramuscular administration for subsequent doses at recommended dose level and determined schedule.
Sponsors
BlueSky Immunotherapies GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of adverse events (AEs) | 7 days | To assess the severity of the adverse event is assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution | 24 weeks | To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in nasal secretion samples by RT-qPCR (copies per ml blood). |
| Virus recovery in oropharyngeal secretion samples | 7 days | To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in oropharyngeal secretion samples by RT-qPCR (copies per sample). |
| Virus recovery in saliva | 7 days | To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in saliva samples by RT-qPCR (copies per sample). |
| Frequency and severity of adverse events (AEs) | 24 weeks | To assess the severity of the adverse event according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. |
| Intralesional T-cell infiltration | 24 weeks | To assess the intralesional T-cell infiltration in tumour tissue available from surgery or biopsy by immunohistological staining. |
| Overall survival (OS) | 60 months | To assess the length of time from the start of treatment or diagnosis until the death of the patient from any cause. |
| Induction of HPV-specific T-cell response following FluBHPVE6E7 administration | 24 weeks | To assess the induction of HPV16 E6- and E7-specific T-cells (%) by IFN-gamma ELISPOT analysis. |
| Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration | 24 weeks | To assess the induction of systemic vector-specific antibodies by HAI assay. |
| Disease-free survival (DFS) | 60 months | To assess the length of time after treatment during which the patient remains free from any signs or symptoms of the disease. |
Countries
Austria
Contacts
Primary ContactMedical University of Vienna
Outcome results
None listed