A study of TG4001 and avelumab cancer immunotherapies in advanced HPV-induced malignancies

Phase 1

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 cancer
MedDRA version: 20.0Level: PTClassification code 10061424Term: Anal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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: 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)
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: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002799-28-GB

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

Inclusion Criteria

• 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 (cervical, vulvar, vaginal, penile, anal cancers and oropharyngeal squamous cell carcinoma of head and neck).
• 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 (i.e., methods with a failure rate of less than 1% per year) during the study period and for 3 months after the last study treatment administration for female patients of childbearing potential (WOCBP) and for male patients who are sexually active with WOCBP
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

Exclusion Criteria

• 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
• Patient 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

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