T-VEC in Non-melanoma Skin Cancer

Study Overview
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Brief Summary
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Evaluation of the mechanism of Action of talimogene laherparepvec (T-VEC) in patients with locally advanced non-melanoma skin cancer.

Detailed Description
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This study evaluates the administration of T-VEC in non-melanoma skin cancer. The aim is to evaluate the effectiveness, safety and tolerability of T-VEC in patients with non-melanoma skin cancer through determination of local immune effects after repeated T-VEC injections.

Official Title
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A Phase I, Open Label, Single Arm, Single Centre Study to Evaluate Mechanism of Action of Talimogene Laherparepvec (T-VEC) in Locally Advanced Non-melanoma Skin Cancer

Conditions
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Non-melanoma Skin Cancer, Basal Cell Carcinoma, Squamous Cell Carcinoma, Cutaneous Lymphoma, Merkel Cell Carcinoma

Intervention / Treatment
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* Genetic: Talimogene Laherparepvec (T-VEC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects Age ≥ 18 years histologically confirmed diagnosis of locally advanced squamous cell carcinoma, basal cell, carcinoma, Merkel cell carcinoma or cutaneous T cell lymphoma at least 1 injectable cutaneous lesion ≥ 20 mm in longest Diameter or multiple injectable lesions that in Aggregate have a longest Diameter of ≥ 50 mm Eastern Cooperative Oncology Group-Status (ECOG Status) 0 or 1 Adequate organ functions Exclusion Criteria: Hypersensitivity to T-VEC or any of ist components Presence of organ and lymph node metastases history or evidence of active autoimmune disease that requires systemic Treatment Evidence of clinically significant immunosuppression active herpetic skin lesions or prior complications hereof pregnancy, breast feeding requires intermittent or chronic systemic Treatment with an antiherpetic drug acute or chronic active Hepatitis B or C infection or HIV infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Talimogene Laherparepvec (T-VEC)<br>Intralesional injections of T-VEC up to 4.0 mL of 10 to the 6 plaque-forming Units/mL (PFU/mL) | Genetic: Talimogene Laherparepvec (T-VEC)<br>* a modified herpes simplex virus-1 (HSV-1) containing the gene coding for human granulocyte macrophage colony-stimulating factor (GM-CSF)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline local immune effects after repeated T-VEC injections | Detection of increased local immune activation markers in skin biopsies of injected lesions. The following markers will be assessed by Polymerase chain reaction (PCR): interferon (IFN), 2-prime, 5-prime oligoadenylate synthetase 1 (OAS1), Interferon-induced GTP-binding protein MxA (MXA) and C-X-C motif chemokine 11 (CXCL11) | at baseline, after 3 injections (week 6) and optionally after 6 injections (week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of Tumor Regression using World Health Organization (WHO) response criteria | Measurement of the treated tumor size will be performed at baseline and at each visit until end of the study | at baseline and at week 22 | 
| Systemic immune response | Detection of increased systemic immune Response markers in sera and peripheral blood mononuclear cells by multi-Color fluorescence-activated cell sorting (FACS) | at baseline and week 6, optionally also at week 12 | 
| Analysis of Adverse events | All serious and non-serious adverse events that occur after enrollment through 30 (+7) days after the last administration of T-VEC will be recorded | At week 1, 4, 6, 8, 10, 12, 14, 16, 18, 22 |