efficacy and safety of talimogene laherparepvec neoadjuvant treatment plus surgery versus surgery alone for melanoma

Conditions: Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma

Summary: 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.

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.

Eligibility criteria:
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