Talimogene Laherparepvec with or without Hypofractionated Radiation Therapy in Treating Patients with Metastatic Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors

Inclusion Criteria

• 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 dimension or exhibits radiotracer uptake consistent with metastasis on positron emission tomography/computed tomography (PET/CT)
• 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 herpes simplex virus (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 talimogene laherparepvec (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 (Common Terminology Criteria for Adverse Events [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