Combo Immunotherapy Effective Against Metastatic Melanoma
Combining the modified virus talimogene laherparepvec with the immunotherapy drug pembrolizumab could improve the response rate of patients with advanced melanoma, according to a recent phase 1b clinical trial.
In their trial, the researchers assessed the safety and efficacy of talimogene laherparepvec combined with pembrolizumab in 21 patients with advanced melanoma. They hypothesized that this combination might change the tumor microenvironment, boost inflammation, and increase CD8+ T cell infiltration.
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Overall, the therapy was well tolerated by patients, who did not experience any dose-limiting toxicities. The most common adverse events reported by patients included fatigue, fevers and chills. The confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria.
Patients who responded to treatment were found to have an increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets of tumors after receiving talimogene laherparepvec therapy. However, the response to the combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature.
“In conclusion, the high response rate in this phase 1 clinical trial and the mechanistic changes documented in patient biopsies suggest that the combination of talimogene laherparepvec and pembrolizumab may be able to overcome some limitations of either single-agent therapy and provide responses beyond what would be expected with either talimogene laherparepvec or pembrolizumab administered alone,” the authors wrote.
The researchers are currently recruiting for a Phase III trial that will include 660 patients and will compare pembrolizumab plus talimogene laherparepvec with pembrolizumab plus an injected placebo.
—Melissa Weiss
Reference:
Ribas A, Dummer R, Puzanov I, et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy [published online September 7, 2017]. Cell. http://dx.doi.org/10.1016/j.cell.2017.08.027.