Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers

Inclusion criteria

• Female or male participants, aged at least 18 years (no upper limit of age)
• ECOG PS 0 or 1
• Life expectancy of at least 3 months
• Participants with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer: cervical, vulvar, vaginal, penile and anal.
• Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression
• Prior therapy:

• No more than one prior systemic treatment for recurrent /metastatic disease
• Prior treatment for recurrent or metastatic disease is not required for:

• Participants with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease
• Participants who are unsuitable for platinum-based therapy
• Participants who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease
• Limited hepatic disease for participants with liver metastases at baseline
• 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 participants if the risk of conception exists during the study period and for 3 months after the last study treatment administration

Exclusion criteria

• Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
• Participants 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 participants 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
• Participants 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
• Participants 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
• Participant with any organ transplantation, including allogeneic stem cell transplantation
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTC), 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
• Participants with known history or any evidence of active interstitial lung disease / pneumonitis
• Participants 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 myocarditis
• 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%)
• Uncontrolled infection