T-VEC in Non-melanoma Skin Cancer

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.

• Talimogene Laherparepvec (T-VEC) (Genetic): a modified herpes simplex virus-1 (HSV-1) containing the gene coding for human granulocyte macrophage colony-stimulating factor (GM-CSF)

Primary outcomes

• Change from Baseline local immune effects after repeated T-VEC injections [at baseline, after 3 injections (week 6) and optionally after 6 injections (week 12)]: 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)

Secondary outcomes

• Detection of Tumor Regression using World Health Organization (WHO) response criteria [at baseline and at week 22]: Measurement of the treated tumor size will be performed at baseline and at each visit until end of the study
• Systemic immune response [at baseline and week 6, optionally also at week 12]: Detection of increased systemic immune Response markers in sera and peripheral blood mononuclear cells by multi-Color fluorescence-activated cell sorting (FACS)
• Analysis of Adverse events [At week 1, 4, 6, 8, 10, 12, 14, 16, 18, 22]: 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

Sex: All, ages: 18 Years to any

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

• Reinhard Dummer, Prof. Dr., Principal investigator, vice-director dermatology