Talimogene laherparepvec (T-VEC) is the first oncolytic immunotherapy to demonstrate therapeutic activity against melanoma in a phase 3 clinical trial, according to a study published online ahead of print in the Journal of Clinical Oncology.1

“T-VEC is an oncolytic virus. It is a genetically modified herpes simplex virus. Scientists modified it so that when it gets into cells, it can grow and multiply in cancer cells but not in healthy cells. It works by being administered directly into the cancer cell and then as it multiplies, it busts open the cell wall and the cancer cell dies,” said Frances Collichio, MD, of the University of North Carolina School of Medicine in Chapel Hill, NC, and one of the study authors in an interview with Cancer Therapy Advisor.

“Also, it has on the back end, the granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the immune system. So the idea is that if you deliver it right to the cancer cell, it can help the body memorize the proteins that part of that cancer cell and then other areas of melanoma might shrink in the course of giving this product.”

For the open-label, phase 3 OPTiM trial, researchers sought to compare T-VEC with GM-CSF in patients with unresected stage 3B to 4 melanoma.

Researchers enrolled 436 patients with unresectable injectable melanoma and randomly assigned them 2:1 to receive T-VEC administered intralesionally or GM-CSF subcutaneously.1

Results showed that the durable response rate was 16.3% (95% CI: 12.1, 20.5) in the T-VEC group compared with 2.1% (95% CI: 0, 4.5) in the GM-CSF group (OR=8.9; P<0.001). Moreover, median overall survival was significantly higher with T-VEC than GM-CSF (23.3 months vs. 18.9 months; HR=0.79; 95% CI: 0.62, 1.00; P=0.051).1

Researchers also found that the overall response rate was 26.4% (95% CI: 21.4, 31.5) with T-VEC versus 5.7% (95% CI: 1.9, 9.5) with GM-CSF. Subgroup analyses demonstrated that response rates were greater in patients receiving T-VEC as first-line therapy compared with receiving it following prior treatment.1

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In regard to safety, the most common adverse events reported with T-VEC treatment were chills (49%), pyrexia (43%), injection site-pain (28%), nausea (36%), influenza-like illness (30%), and fatigue (50%).1

“The overall serious toxicity is very low. Flu-like symptoms last for only a day or two. Patients could get cellulitis but that was only seen in 2% of patients.”

“This is a treatment that is very effective in patients with locally advanced disease and is very safe,” Dr. Collichio said. “It’s very different from any other immune treatment out there. There is no other oncolytic treatment that has been approved this year.”

Although this is the first oncolytic immunotherapy to demonstrate therapeutic benefit in patients with locally advanced melanoma, in the last year, the U.S. Food and Drug Administration has approved two monoclonal antibodies, pembrolizumab and nivolumab, for the treatment of patients with  unresectable or metastatic melanoma and disease progression following ipilimumab.

According to the American Cancer Society, nearly 74,000 new melanomas will be diagnosed in the United States in 2015, and approximately 10,000 people with melanoma are expected to die of the disease.2

References

  1. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015. [Epub ahead of print] doi: 10.1200/JCO.2014.58.3377.
  2. What are the key statistics about melanoma skin cancer? American Cancer Society website. http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statistics. Updated March 20, 2015. Accessed July 1, 2015.