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