Amgen’s virus therapy against metastatic malignant melanoma, Imlygic, appears to boost the effects of Yervoy (ipilimumab), according to the results of a Phase 2 clinical trial published in the Journal of Clinical Oncology.
The combination more than doubled the percentage of patients who saw their tumors shrink compared to those treated with Yervoy alone. Yervoy is manufactured by Bristol-Myers Squibb. The treatment also caused tumor lesions not directly injected with the drug to shrink, demonstrating a response triggered throughout the body.
Imlygic (talimogene laherparepvec) is a genetically modified live oncolytic herpes virus that kills cancer cells by infecting and rupturing them.
“Advanced melanoma is highly aggressive and can require multiple treatment approaches over the course of the disease,” Jason Chesney, MD, lead author of the study and director of the James Graham Brown Cancer Center at the University of Louisville, said in a press release.
“Results from the study found that administration of Imlygic in combination with ipilimumab led to greater efficacy versus ipilimumab alone in both uninjected and visceral lesions. These data show that this combination of a checkpoint inhibitor plus Imlygic demonstrated a synergistic clinical effect and enhanced antitumor immune response in patients with metastatic melanoma,” Chesney added.
The Phase 2 trial (NCT01740297) enrolled nearly 200 patients with previously untreated metastatic melanoma that was judged unsuitable for surgical removal. It compared the combination of Imlygic and Yervoy with Yervoy alone.
The study, “Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma,” showed that 39% of patients in the combination group responded to the treatment with shrinking tumors. Among those given Yervoy alone, that percentage was 18%.
The Imlygic and Yervoy combination also triggered more complete responses, eradicating tumors in 13% of patients compared with 7% in the Yervoy-only group.
Researchers are not sure how the two drugs complement each other to boost the response. It is possible that the rupture of cancer cells gives rise to higher levels of so-called cancer antigens, which are molecules that are targeted by the immune reactions unleashed by the actions of Yervoy. Yervoy is a checkpoint-blocking drug targeting the protein receptor CTLA4.
The combo treatment also causes the release of GM-CSF, an immune mediator that may contribute to the initiation of an anti-tumor response.
Results showed that the combination treatment managed to shrink tumor lesions in inner organs in more than half of patients with such metastases, and also improved progression-free survival from 6.4 months on Yervoy to 8.2 months on the combination of the two. While the difference was not statistically significant, researchers said analyses — including those of overall survival — are still ongoing.
The combination did appear to cause certain side effects that were more prevalent than in the Yervoy group alone. These included fatigue, chills, diarrhea, itches, rash, and nausea.
“The data published today in the Journal of Clinical Oncology supports the scientific hypothesis behind the combination of Imlygic with an immune checkpoint inhibitor. We are excited about the promise of our diverse immuno-oncology pipeline that looks at combinations that may be effective in stimulating an immune attack on cancer cells,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.
Imlygic is currently approved in the U.S. and Europe for the treatment of melanoma lesions in the skin and lymph nodes, but not for lesions in inner organs.