Rresults 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 ) were presented.
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% in the Talimogene Laherparepvec arm versus 2% in the GM-CSF arm ( p less than 0.0001 ).
The overall response rate was 26% with Talimogene Laherparepvec as compared to 6% for GM-CSF. A trend toward overall survival ( HR=0.79 ) was also observed at a predefined interim analysis.
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% in stage IIIB/IIlC, 16% in stage IVM1a, and 3 and 8%, respectively, for stages IVM1b and IVM1c.
The DRR with GM-CSF was not higher than four percent in any of the stage subsets.
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% of Talimogene Laherparepvec patients and 13% 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, and stimulating a systemic anti-tumor immune response.
Talimogene Laherparepvec is injected directly into tumor 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 tumor 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.
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.
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. Currently, 132,000 melanoma cases occur globally each year. In the United States, while melanoma accounts for less than 5% of skin cancer cases, it causes the most skin cancer deaths. The number of new cases of melanoma in the U.S. has been increasing for the last 30 years.
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. ( Xagena )
Source: Amgen, 2013