A Study of T-VEC (Talimogene Laherparepvec) With or Without Radiotherapy for Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Inclusion Criteria:

* Man or woman ≥ 18 years old
* Life expectancy \> 4 months
* Histopathologically confirmed melanoma, Merkel cell carcinoma or other solid tumor malignancy
* Cutaneous subcutaneous soft tissue, or superficial lymphatic metastasis not suitable for surgical resection
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* Cutaneous subcutaneous soft tissue, or superficial lymphatic metastasis that is amenable to injection and irradiation and \> 10 mm in longest dimension

  ° Cutaneous metastasis in a region of previous radiation therapy is amenable to radiation therapy as part of this protocol if at least 6 months has elapsed since prior radiotherapy and the dose of radiotherapy previously administered did not exceed an equivalent dose of 60 Gy in 2 Gy equivalent fractions at the skin surface (using linear-quadratic modeling with alpha/beta=11.5)
* Metastasis that is \> 10 mm in longest dimensionor exhibits radiotracer uptake consistent with metastasis on PET/CT
* Adequate coagulation function (platelet count \>50 k/mcL, international normalized ratio of \< 1.5)
* Resolution or stabilization of clinically significant adverse events from prior therapy
* Able to provide valid written informed consent

Exclusion Criteria:

* Active herpetic skin lesions or prior complications of HSV-1 infection (such as herpetic keratitis, herpetic encephalitis)
* Receipt of a therapeutic anticoagulant
* Receipt of live vaccine within 28 days of planned first dose of TVEC
* Receipt of another cancer therapy (targeted therapy, chemotherapy, investigational therapy, immunotherapy, radiotherapy or surgery) which is yielding an overall response (by response criteria in this study)

  ° Patients with stable or progressing disease (as determined by at least 2 consecutive assessments at 6-week interval) can continue to receive the same therapy during treatment as part of this protocol
* History of symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease, ulcerative colitis) requiring systemic treatment (for example corticosteroids or immunosuppressants); replacement therapy (for example, thyroxine, insulin) is not considered a systemic treatment
* History of high grade (CTCAE ≥ Grade 3) immune mediated adverse event from prior cancer immunotherapy
* History of CTCAE ≥ Grade 2 immune mediated endocrinopathy from prior cancer immunotherapy
* Intermittent or chronic use of oral or intravenous antiherpetic drug (such as acyclovir)
* Active or chronic hepatitis B or C infection

  ° Previously infected, with evidence of immunity and no evidence of active hepatitis is not an exclusion criterion
* Known human immunodeficiency virus (HIV) infection
* Known leukemia or lymphoma
* Common variable immunodeficiency
* Patients requiring chronic high dose immunosuppressants including steroids (prednisone daily equivalent of ≥ 10 mg)
* Known severe congenital or acquired cellular or humoral immunodeficient or immunocompromised patients
* High likelihood of protocol non-compliance (in opinion of investigator)
* Woman of childbearing potential unwilling to use effective contraception during protocol treatment and for 3 months after last dose of Talimogene Laherparepvec
* Woman of childbearing potential that is pregnant or breast-feeding, or planning to become pregnant or breast-feed during protocol treatment and for 3 months after last dose of Talimogene Laherparepvec