The results of the pivotal OPTiM study have shown that Talimogene laherparepvec monotherapy is the first oncolytic immunotherapy to demonstrate therapeutic benefit in a phase 3 trial for patients with metastatic melanoma.
Talimogene laherparepvec is an investigational oncolytic immunotherapy 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. Then, the rupture of the cancer cells can release tumor-derived antigens, along with granulocyte-macrophage colony-stimulating factor ( GM-CSF ), which 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.
Study 005/05, referred to as OPTiM, was a phase 3, multicenter, open-label, randomized clinical trial comparing Talimogene laherparepvec to GM-CSF in patients with advanced melanoma ( stage IIIB, IIIC, or IV ) that was not surgically resectable.
The primary endpoint of the study was durable response rate ( DRR ).
In the 436-patient study, Talimogene laherparepvec has significantly improved durable response rate with 16.3% of Talimogene laherparepvec patients achieving a complete response ( CR ) or partial response ( PR ) within the first 12 months of treatment and maintaining it continuously for at least six months compared to 2.1% of patients treated with GM-CSF ( p less than 0.001 ).
The OPTiM study has also provided additional secondary and exploratory data that have demonstrated the effects of Talimogene laherparepvec in patients with stage III/IV metastatic melanoma, including:
improved overall ( CR + PR ) response rate compared with GM-CSF, 26.4% vs. 5.7%, respectively. In particular, the CR rate was higher in the Talimogene laherparepvec arm than in the GM-CSF arm ( 10.8% vs. 0.7%, respectively );
a strong trend in overall survival. The median overall survival was 4.4 months longer in the Talimogene laherparepvec arm than in the GM-CSF arm ( hazard ratio, HR=0.79; p=0.051 );
evidence of a systemic effect. Eight of 71 patients ( 11.3% ) with visceral lesions that could not be injected ( predominately in the lung and liver ) had an overall decrease in those lesions of more than 50%.
The most commonly reported treatment-related adverse events were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection-site pain. Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common serious adverse reaction was cellulitis. ( Xagena )
Source: Amgen, 2015