Amgen (NASDAQ: AMGN) today announced detailed results from a pivotal Phase 3 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 (Abstract No. LBA9008).
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 percent in the talimogene laherparepvec arm versus two percent in the GM-CSF arm (95 percent CI, 12-21 percent, versus 95 percent CI, 0-5 percent, p<0.0001). The overall response rate was 26 percent with talimogene laherparepvec as compared to six percent for GM-CSF. A trend toward overall survival (HR = 0.79, 95 percent 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 , M.D., executive vice president of Research and Development at Amgen. "We are pleased with the results of this pivotal Phase 3 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 percent in stage IIIB/IIlC, 16 percent in stage IVM1a, and three and eight percent respectively for stages IVM1b and IVM1c. The DRR with GM-CSF was not higher than four percent 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 , M.D., 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 percent of talimogene laherparepvec patients and 13 percent 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 tumors while also stimulating a systemic anti-tumor immune response.
Full results will be presented today at the 2013 ASCO Annual Meeting at the Melanoma/Skin Cancers session on Saturday, June 1, 3:45 p.m. CDT, S406 (Abstract No. LBA9008).
Trial Design
This trial was a global, randomized, open-label, Phase 3 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.
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