Talimogene laherparepvec (T-VEC), a herpes simplex virus type 1–derived oncolytic immunotherapy, improved durable response rate (DRR) and overall survival (OS) in patients with advanced melanoma in a randomized, prospective phase 3 trial.1

T-VEC was derived from herpes simplex type 1 by deleting 2 viral genes and further modified by encoding the human gene for granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF boosts the body’s immune response while the virus selectively replicates in tumor tissue following local injection.

“Part of the importance of this data is that it is one of the first oncolytic viruses to really ever go into a randomized phase 3 study,” said Howard L. Kaufman, MD, FACS, of the Rutgers Cancer Institute of New Jersey in New Brunswick during an interview with Cancer Therapy Advisor.

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Dr Kaufman said this study definitively establishes the legitimacy of oncolytic viruses in cancer therapy, which will allow research in other types of viruses and in approaches where other viral vectors can be combined. “I think we’re going to have to take it outside of melanoma and theoretically to any cancer that we can access,” he said.

The study enrolled 436 patients with advanced melanoma. They were randomly assigned to receive intralesional T-VEC (295 patients) or subcutaneous GM-CSF (141 patients). The primary endpoint was DRR, and secondary endpoints included OS, best overall response and tumor burden, onset and duration of response, and time to treatment failure.

DRR was 16.3% for the T-VEC arm and 2.1% for the GM-CSF arm. Median OS was 23 months with T-VEC and 18.9 months with GM-CSF.

“It’s very challenging to design a clinical trial for something that is basically a new class of drugs,” said Dr Kaufman. “And there is no doubt in my mind that at the primary endpoint there is clinical activity with this agent. I also think an important point is that the toxicity profile is very tolerable.”

There were few reported grade 3 or 4 toxicities in the study, and the most frequently occurring adverse events in the T-VEC arm were fatigue, chills, and pyrexia.

“I think T-VEC is going to be a very good agent in combination because of its safety profile,” said Dr Kaufman.

He said he anticipates that this T-VEC will provide clinical oncologists with more treatment options soon. “It offers patients another option, and if they don’t respond to more established therapies, this gives them something else that is well tolerated and has been associated with very good response rates,” he said.