A study of TG4001 and avelumab cancer immunotherapies in advanced HPV-induced malignancies
- Conditions
- HPV-16 positive recurrent or metastatic malignancies including oropharyngeal squamous cell carcinoma of head and neck, cervical cancer, vulvar cancer, vaginal cancer, penile cancer, anal cancerMedDRA version: 20.0Level: PTClassification code 10061424Term: Anal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10047777Term: Vulvar cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10046888Term: Vaginal cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: PTClassification code 10034299Term: Penile cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2016-002799-28-ES
- Lead Sponsor
- Transgene
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 52
• Written informed consent.
• Female or male patients, aged at least 18 years (no upper limit of age)
• ECOG PS 0 or 1
• Life expectancy of at least 3 months
• Patients with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer. Phase Ib: cervical, vulvar, vaginal, penile, anal, and oropharyngeal squamous cell carcinoma of head and neck. Phase II part: an expansion cohort of oropharyngeal SCCHN will be included
• Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression
• Prior therapy: Patients MAY have received up to 2 prior lines of systemic chemotherapy for the management of metastatic or recurrent disease; for SCCHN, patients MUST have previously been exposed to platinum-based therapy, either as part of definitive chemo-radiation OR as first line systemic treatment for metastatic disease which may include cetuximab. Patients with recurrence/progression within 6 months of prior multimodal therapy using platinum-based therapy are eligible. Patients with cervical cancer may have undergone surgery and/or received definitive radiation or chemo-radiation therapy for localized disease.
• Availability of tumor tissue from biopsy
• At least one measurable lesion by CT scan according to RECIST 1.1.
• Adequate hematological, hepatic and renal function
• Negative blood pregnancy test at screening for women of childbearing potential
• Highly effective contraception for both male and female patients if the risk of conception exists during the study period and for 3 months after the last study treatment administration
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
• Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
• Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to = 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed
• Patients with CNS metastases except those with brain metastases treated locally and clinically stable during 4 weeks prior to start of study treatment, and those without ongoing neurological symptoms that are related to the brain localization of the disease
• Other active malignancy requiring concurrent systemic intervention
• Patients with previous malignancies other than the target malignancy to be investigated in this trial (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Patients with any organ transplantation, including allogeneic stem cell transplantation
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTC V4.03), any history of anaphylaxis, or uncontrolled asthma
• Any known allergy or reaction to eggs, gentamycin or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products
• Any known allergy or reaction to any component of anti-PD-L1/PD-1 or its excipients
• Patients with history of interstitial lung disease
• Patients with active, known, or suspected auto-immune disease or immunodeficiency, except type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment
• Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction (< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class = II), or serious uncontrolled cardiac arrhythmia requiring medication/active intervention
• History of uncontrolled intercurrent illness including but not limited to:
- Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower)
- Uncontrolled diabetes (e.g., hemoglobin A1c = 8%)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method