Efficacy and Safety of Talimogene Laherparepvec Neoadjuvant Treatment Plus Surgery Versus Surgery Alone for Melanoma

This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of
talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery
alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma.

Arm 1: Talimogene laherparepvec for 6 doses followed by surgical resection of melanoma tumor
lesion(s).

Arm 2: Immediate surgical resection of melanoma tumor lesion(s) Following surgery, adjuvant
systemic therapy and/or radiotherapy may be administered at the investigator's discretion and
per the institutional standard of care.

Subjects will be followed for safety approximately 30 (+15) days after surgery and for
disease recurrence, subsequent anticancer therapy, and survival every 3 months (±30 days) for
first 3 years after the end of the safety follow-up period and then every 6 months (±30 days)
until death, subject withdraws full consent, or up to 5 years after the last subject is
randomized.

Inclusion Criteria:

- Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for
complete surgical resection.

- Prior systemic, regional and radiation anticancer therapies for melanoma must have
been completed at least 3 months prior to randomization.

- Subject must have measurable disease and must be a candidate for intralesional therapy
with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10
mm in longest diameter) or with multiple injectable lesions that in aggregate have a
longest diameter of ≥ 10 mm.

- Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1 and must have a serum lactate dehydrogenase (LDH) ≤ 1.0 X upper limit of normal
and adequate hematologic, hepatic, renal, and coagulation organ function- Other
criteria may apply

Exclusion Criteria:

- Subject must not have primary ocular or mucosal melanoma, or history or evidence of
melanoma associated with immunodeficiency states (eg, hereditary immune deficiency,
organ transplant, or leukemia).

- Subject must not have history or evidence of symptomatic autoimmune pneumonitis,
glomerulonephritis, vasculitis, or other symptomatic autoimmune disease.

- Subject must not have evidence of clinically significant immunosuppression or active
herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1)
infection (eg, herpetic keratitis or encephalitis) and must not require intermittent
or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than
intermittent topical use.

- Subject known to have acute or chronic active hepatitis B, hepatitis C, or human
immunodeficiency virus infection will also be excluded.

- Subject must not have been treated previously with talimogene laherparepvec or tumor
vaccine.

Other criteria may apply