Amgen has presented detailed results from a pivotal phase III trial evaluating talimogene laherparepvec in patients with unresected stage IIIB, IIIC or IV melanoma compared to granulocyte-macrophage colony-stimulating factor (GM-CSF). The results will be presented as an oral presentation at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

The study met its primary endpoint of durable response rate (DRR), defined as the rate of complete or partial response lasting continuously for at least six months. A statistically significant difference was observed in DRR with 16 per cent in the talimogene laherparepvec arm versus two per cent in the GM-CSF arm (95 per cent CI, 12-21 per cent, versus 95 per cent CI, 0-5 per cent, p<0.0001). The overall response rate was 26 per cent with talimogene laherparepvec as compared to six per cent for GM-CSF. A trend toward overall survival (HR = 0.79, 95 per cent CI, 0.61-1.02) was also observed at a predefined interim analysis.

"These are the first data from a controlled trial of oncolytic immunotherapy to demonstrate activity in melanoma," said Sean E Harper, MD, executive vice president of Research and Development at Amgen. "We are pleased with the results of this pivotal phase III trial for talimogene laherparepvec and we look forward to the mature overall survival data later this year."

In regionally and distantly metastatic melanoma (stages III and IV), cancer has spread to skin, lymph nodes, or to other organs distant from the site of origin. The DRR was highest among patients with stage III and stage IVM1a disease. The observed DRR for talimogene laherparepvec were: 33 per cent in stage IIIB/IIlC, 16 per cent in stage IVM1a, and three and eight per cent respectively for stages IVM1b and IVM1c. The DRR with GM-CSF was not higher than four per cent in any of the stage subsets.

"Over the last 30 years, the incidence of metastatic melanoma has increased by over 200 percent, so there is a need for new treatment options," said study author Robert Andtbacka, MD, assistant professor, University of Utah Huntsman Cancer Institute. "The results of this study are encouraging in a disease as devastating as metastatic melanoma."

The most frequently observed adverse events were fatigue, chills and pyrexia. The most common serious adverse events include disease progression, cellulitis and pyrexia. Serious adverse events occurred in 26 per cent of talimogene laherparepvec patients and 13 per cent of GM-CSF patients.

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to work in two important and complementary ways - causing local lytic destruction of tumours while also stimulating a systemic anti-tumour immune response.

This trial was a global, randomized, open-label, phase III trial to evaluate the safety and efficacy of talimogene laherparepvec compared to a control therapy with GM-CSF in over 400 patients with unresected stage IIIB, IIIC or IV melanoma.

Patients were randomized 2:1 to receive either talimogene laherparepvec intralesionally every two weeks or GM-CSF subcutaneously for the first 14 days of each 28 day cycle. Treatment could last for up to 18 months. Where appropriate, stable or responding patients could receive additional treatment on an extension protocol.

Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin. Melanoma is the most aggressive and serious form of skin cancer. Melanoma is considered to be advanced when it has spread, or metastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs, or other parts of the body distant from the primary lesion site.

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumor tissue. Talimogene laherparepvec is injected directly into tumour tissue and then replicates until the membrane of the cancer cells rupture, thereby destroying the cells, in a process known as cell lysis. The virus that was contained in these cells is then released locally in the tumour tissue along with GM-CSF, a white blood cell growth factor that the virus is engineered to express. This is intended to lead to the activation of a systemic immune response to kill tumor cells throughout the body.

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