The immune-therapy drug ipilimumab, together with talimogene laherparepvec or T-VEC, showed positive results in a Phase 1b clinical trial of metastatic melanoma patients who did not respond to other treatments and whose tumors could not be surgically removed.
The study, “Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma,” was published in the Journal of Clinical Oncology.
“Tumor immunotherapy has become an established treatment of metastatic melanoma and is being increasingly applied to other cancer types,” the authors wrote. “A hallmark of tumors likely to respond to immunotherapy is a lymphocyte-predominant tumor microenvironment. To date, immunotherapy designed to promote lymphocyte accumulation within established tumors, activate lymphocyte function and cytotoxicity, and prevent T-cell suppression has shown the most promise.”
The trial included 19 participants, ages 29-84 with stage IIIB or stage IV metastatic melanoma, and the therapeutic combination was directly injected into patients’ tumors.
An objective response rate (ORR) of 50% was observed, with four patients (22 percent) obtaining a complete response and remaining in remission one year after the treatment. Five patients (28 percent) obtained a partial response, and four patients remained stable.
A response was observed in injected and not injected lesions. A total of 11 injected lesions (31 percent) regressed completely, while 26 (74 percent) regressed by at least half. Among uninjected lesions, nine (39 percent) showed complete regression and 12 (52 percent) regressed by at least half.
Researchers concluded that the combination of T-VEC with immune checkpoint inhibitors such as ipilimumab might represent a potential therapy option for patients with metastatic melanoma that cannot be treated with surgery.
A Phase 2 clinical trial comparing the effects of ipilimumab plus T-VEC to ipilimumab treatment alone is also underway in patients with metastatic melanoma.
Ipilimumab is a cytotoxic T-cell antigen-4 inhibitor, and acts by turning off the mechanisms that inhibits T-cells from functioning normally and destroying tumor cells.
T-VEC is an active immunotherapy agent derived from the herpes simplex virus type 1, the virus causing cold sores around the mouth and lips. It addition to directly attacking tumor cells, it also acts by secreting a cell-signaling molecule called GM-CSF to initiate an immune response specifically targeting tumor cells.