T-VEC for Advanced Melanoma Treatment Approved

The US Food and Drug Administration has approved the first-in-class oncolytic immunotherapy talimogene laherparepvec (T-VEC; lmlygic) to treat unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

T-VEC is created through genetic alterations of the herpes simplex 1 virus to secrete the cytokine GM-CSF in the tumor resulting in cell lysis.

The approval followed results from the phase III OPTiM study, which randomized 436 patients with unresected stage IIIB/C and IV melanoma to receive either intralesional T-VEC (≤ 4 mL x106 PFU/mL for 3 weeks followed by ≤ 4 mL x108 PFU/mL every 2 week) or subcutaneous GM-CSF (125 µg/m2 every 14 days in a 28-day cycle).

Durable response rates (DRR) was the primary endpoint, with overall survival (OS) as the secondary endpoint. According to the study results, DRR was 16.3% with T-VEC while only 2.1% for GM-CSF. Furthermore, differences in DRR were more evident in patients who had stage IIIB/C melanoma.

There were a total of 12 patient deaths within 30 days of the last dose of T-VEC, including 10 in the primary OPTiM study and two in an extension of the study. Nine of the deaths were associated with progressive disease, while the remaining three were from myocardial infarction, cardiac arrest, and sepsis. There were four patient deaths in the GM-CSF arms, two each in the primary and extension analyses.

Also, The most commonly reported adverse events were fatigue, chills, pyrexia, nausea, influenza0like illness, and injection site pain. Additionally, disease progression and cellulitis were the most prevalent of serious adverse events.

Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement, “Imlygic is the first clinical and regulatory validation of an oncolytic virus as a therapy, which Amgen is proud to bring to patients with a serious form of skin cancer. Not all melanoma patients currently benefit from available therapies, and Imlygic represents an important new option that can provide meaningful durable responses for patients with this aggressive and complex disease.”

Several clinical trials are underway to study effective combination treatment with T-VEC. A phase I/II study is assessing T-VEC with ipilimumab for unresected melanoma (NCT01740297) and a phase III study is observing T-VEC with pembrolizumab for unresected melanoma (NCT02263508).

“Immunotherapy is an exciting area for cancer research, and we are currently studying lmlygic in combination with other immunotherapies in advanced melanoma and other solid tumors,” concluded Harper.