Systemic tumor-specific immune response elicited by an oncolytic immunotherapy.
The novel immunotherapy talimogene laherparepvec (TVEC) has become the first oncolytic virus to successfully complete a phase III trial in advanced melanoma, according to the drug’s developer, Amgen.
In the trial, TVEC, a genetically modified version of herpes simplex virus type 1, was compared to granulocyte-macrophage colony-stimulating factor (GM-CSF) as a treatment for patients with advanced melanoma. Overall, the study met its primary endpoint with a significant improvement in durable response rate (DRR) in the TVEC arm. The data showed an overall survival (OS) trend favoring TVEC.
Although not a standard treatment for melanoma, GM-CSF was used as the comparator in this trial due to TVEC’s mechanism of action. When injected into the tumor, TVEC is able to replicate until it causes tumor cell lysis. Upon lysis, the engineered virus expresses GM-CSF in the tumor tissue, with the goal of stimulating a systemic immune response and killing tumor cells throughout the body.
“These are the first phase III results of this novel approach to cancer therapy,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen, in a statement. “A high unmet need exists in melanoma and we believe the innovative mechanism of action of talimogene laherparepvec may offer a promising approach for these patients.”
In the phase III trial, 439 patients with unresected stage IIIB, IIIC, or IV melanoma were randomized 2:1 to receive either TVEC or subcutaneous GM-CSF. The primary endpoint, DRR, was defined as the rate of complete or partial response lasting for 6 or more months.
The DRR rate in the TVEC arm was 16% compared with 2% in the GM-CSF arm. Data for an analysis of the secondary endpoint of OS has not yet matured, but is trending in favor of TVEC. According to Amgen, mature OS data are expected to become available in late 2013.
The most common serious adverse events were disease progression, cellulitis, and pyrexia. Additional safety and efficacy data are expected to be presented at the 2013 ASCO Annual Meeting.