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: 20.0 Level: PT Classification code 10061424 Term: Anal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10034299 Term: Penile cancer System Organ Class: 10029104 - Neoplasms benign
Conditions
Interventions
Product Name: MVA-HPV-IL2
Product Code: TG4001
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Tipapkinogene sovacivec
Current Sponsor code: MVATG8042
Other descriptive name: MVATG8
Sponsors
Transgene
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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
Exclusion criteria
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 • 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%)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase Ib: safety and tolerability Phase II: overall response rate according to RECIST 1.1;Main Objective: Phase Ib objective: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies. Phase II objective: To evaluate the efficacy of TG4001 combined to avelumab in terms of Overall Response Rate (ORR) by using RECIST 1.1 in the expansion cohort of oropharyngeal recurrent or metastatic squamous cell carcinoma of head and neck.;Secondary Objective: To evaluate the combination of TG4001 and avelumab with respect to: • Overall response rate (ORR) by using RECIST 1.1 (phase Ib part) • Progression Free Survival (PFS) • Overall Survival (OS) • Duration of Response (DoR) • Disease control rate (DCR) • Safety profile (phase II part);Timepoint(s) of evaluation of this end point: Phase Ib: - The safety data will be collected and evaluated by the Investigators and the sponsor on an ongoing basis. - Dose limiting toxicity will be assessed in each included and treated patient during the first 4 weeks. - A SRC will meet before each new cohort begins to analyse and review the safety data of all patients in the previous cohort. - At the end of the phase Ib, the safety data of all patients will be analyzed and discussed with the SRC which will make recommendation to the sponsor on the conduct of the study. Phase II: Tumor response will be evaluated at baseline and then every 6 weeks until disease progression. Beyond 9 months after start of treatment, tumor evaluation will be performed every 12 weeks until disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib: Overall response rate by using RECIST 1.1 and overall safety profile Phase II: - Progression Free Survival (PFS) - Overall Survival (OS) - Duration of Response (DoR) - Disease control rate (DCR) - Overall safety profile;Timepoint(s) of evaluation of this end point: In both phase of the study, tumor assessment will be performed locally according to investigator’s assessment every 6 weeks from the start of study treatment until disease progression or for a period of 9 months after start of study treatment, whichever occurs first. Beyond 9 months after start of study treatment, the evaluations will be performed every 12 weeks until disease progression. The overall safety profile will be assessed during the conduct of the trial. | — |
Countries
Spain
Contacts
Public ContactMedical Affairs Secretariat
Transgene
Outcome results
None listed