Amgen recently announced top-line results from the primary overall survival analysis of a phase III trial in melanoma, which evaluated the efficacy and safety of talimogene laherparepvec (also known as T-VEC) for the treatment of unresected stage IIIB, IIIC, or IV melanoma compared to treatment with subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF, Leukine). Talimogene laherparepvec, an oncolytic immunotherapy, is derived from herpes simplex virus type 1. The drug is designed to selectively replicate within tumors and to produce GM-CSF to enhance systemic antitumor immune responses.
The global, randomized, open-label phase III trial enrolled patients with unresected stage IIIB, IIIC, or IV melanoma. Patients were randomized 2:1 to receive either talimogene laherparepvec every 2 weeks through direct tumor injection, or GM-CSF subcutaneously for the first 14 days of each 28-day cycle, for up to 18 months. Results showed that, while the primary endpoint of durable response rate was met (as previously reported), the secondary endpoint of overall survival was not met (P = .051). The estimated overall survival hazard ratio and improvement in median overall survival were similar to what was previously reported at the interim analysis.
Survival Trend Warrants Further Research
“We remain encouraged that the study met its primary endpoint of achieving durable responses in patients with metastatic melanoma,” said Sean E. Harper, MD, Executive Vice President of Research and Development at Amgen. “We missed statistical significance on the secondary endpoint of overall survival but the strong trend in survival benefit supports further research of talimogene laherparepvec to better understand its role in melanoma, both as a single-agent and in combination with other therapies.” The most frequent adverse events observed in this trial were fatigue, chills, and pyrexia. The most common serious adverse events include disease progression, cellulitis, and pyrexia. ■