Amgen announced interim overall survival (OS) 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). Results were presented this week during an oral session at the 2013 Society for Melanoma Research (SMR) Congress, in Philadelphia.
At a predefined interim analysis of this phase 3 study, median OS was 23.3 months in the talimogene laherparepvec arm over 19.0 months in the GM-CSF arm. Differences in survival rates were pronounced in the subset of patients with stage IIIB, IIIC or IV M1a disease or who received talimogene laherparepvec as first-line treatment, each comprising approximately 50% of the study population.
"The interim overall survival subset results complement the durable response data we reported earlier this year and these endpoints appear to correlate with each other in terms of where the most benefit is being seen in this trial," said Sean E. Harper, MD, executive vice president of research and development at Amgen. "We look forward to the mature overall survival data expected in the first half of next year."
The most frequently observed adverse events were fatigue, chills and pyrexia. The most common serious adverse events include disease progression in both arms, and cellulitis and pyrexia in the talimogene laherparepvec arm. Serious adverse events occurred in 26% of talimogene laherparepvec patients and 13% of GM-CSF patients. Immune-mediated events were reported infrequently.
"A favorable trend in overall survival was observed in patients who received talimogene laherparepvec and the trend was pronounced in patients with stage III and IV M1a disease where an important clinical need exists for patients whose disease has not yet spread to distant organs," said Howard Kaufman, MD, professor and director of the section of surgical oncology in the Department of General Surgery, Rush University Medical Center in Chicago. "I look forward to seeing the final results next year."
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.
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumor tissue and to initiate a systemic antitumor immune response. Talimogene laherparepvec is injected directly into tumor tissue and is intended to replicate preferentially in tumor cells causing lytic cell death and releasing an array of tumor specific antigens.
Talimogene laherparepvec is also engineered to express GM-CSF, a white blood cell growth factor that can help to activate the immune system. The aim of this combination of actions is to induce a systemic antitumor immune response that targets tumor cells throughout the body.
Date: November 18, 2013