Date: 2014-06-02
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Amgen (USA - CA)
Product: talimogene laherparepvec
Action
mechanism: oncolytic virus. Talimogene laherparepvec is derived from an herpex simplex virus-1 that has been genetically engineered to infect
and replicate within cancer cells and to produce the protein GM-CSF. This oncolytic immunotherapy has been designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor's cells causing the cell to rupture and die in a process called lysis. The rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.
Disease: metastatic melanoma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The Phase 1b/2, multicenter, open-label trial enrolled patients with unresected Stage IIIB-IV melanoma (58 percent of patients were Stage IV), no prior systemic treatment, measurable disease, and more than one injectable cutaneous, subcutaneous or nodal lesion (n=19). Talimogene laherparepvec was administered by intratumoral injection on day 1 of week 1, day 1 of week 4, and then every two weeks thereafter. Ipilimumab was administered intravenously on day 1 of week 6, week 9, week 12, and week 15 for a total of four infusions. Patients were treated with talimogene laherparepvec until complete response, all injectable tumors disappeared, disease progression per a modified immune-related response criteria (irRC), or intolerance of study treatment.
The Phase 3 pivotal trial was a global, randomized, open-label trial to evaluate the safety and efficacy of talimogene laherparepvec compared to a control therapy (GM-CSF) in over 400 patients with unresected stage IIIB, IIIC or IV melanoma. The primary endpoint was durable response rate defined as the rate of complete response or partial response lasting continuously for six or more months, as compared to control therapy. Overall survival was a secondary endpoint. 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.
Latest
news: * On June 2, 2014, Amgen announced new data from two key clinical trials that support the potential of talimogene laherparepvec, a novel, investigational oncolytic immunotherapy, as both a single agent and as part of a combination regimen in patients with metastatic melanoma. The findings were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Data from the 19 patients in the Phase 1b combination study, presented for the first time at ASCO , showed no dose-limiting toxicities with talimogene laherparepvec in combination with ipilimumab (Abstract #9029). Additionally, tumors either shrank in size or were no longer detectable in 56 percent of patients when talimogene laherparepvec was given prior to and in combination with ipilimumab. The most common adverse events observed were chills, fevers, rash and fatigue. As previously reported, the pivotal Phase 3 trial met its primary endpoint showing a statistically significant improvement in durable response rate (16 percent in the talimogene laherparepvec arm versus two percent in the granulocyte-macrophage colony-stimulating factor [GM-CSF]). Among the 26 percent of patients who achieved an overall response (n=78) in the talimogene laherparepvec arm, 40 percent achieved a complete response (no evidence of disease). Data presented today showed that among the talimogene laherparepvec responders, there was a 65 percent probability of responses lasting for at least 12 months. Detailed results of the overall survival analysis, a key secondary endpoint of the pivotal Phase 3 trial evaluating talimogene laherparepvec as a single agent, were also presented (Abstract #9008a). The results demonstrated a 4.4 month improvement in overall survival (HR=0.79;p=0.051) which closely approached statistical significance in the total patient population tested that included patients with and without visceral tumors (tumors involving solid organs such as the lungs and liver).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.
