Oncolytic Virus Plus Ipilimumab Improves Responses in Advanced Melanoma


The combination of an oncolytic virus with ipilimumab yielded a significantly higher response rate vs ipilimumab alone in patients with advanced melanoma.

The combination of an oncolytic virus known as talimogene laherparepvec with ipilimumab yielded a significantly higher response rate than ipilimumab alone in a phase II study of patients with advanced melanoma. This was the first randomized trial to test such a combination.

Talimogene laherparepvec is a genetically modified herpes simplex virus type 1; it expresses the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor. “Talimogene laherparepvec and ipilimumab enhance T-cell activation through different mechanisms,” wrote study authors led by Jason Chesney, MD, PhD, of the J. Graham Brown Cancer Center at the University of Louisville in Kentucky. “Talimogene laherparepvec is designed to increase tumor-specific immune activation by improving antigen presentation and T-cell priming, whereas CTLA-4 blockade with ipilimumab promotes T-cell expansion.”

The new study included 198 patients with advanced melanoma. Patients with BRAF wild-type melanoma could have received one prior line of systemic therapy, and BRAF-mutant patients could have received two prior lines. They were randomized to receive either talimogene laherparepvec plus ipilimumab (98 patients) or ipilimumab alone (100 patients). The results were published in the Journal of Clinical Oncology.

The baseline characteristics of the patients were well balanced between the groups. The median age was 65 years in the combination group and 64 years in the monotherapy group, and approximately 70% of patients had an ECOG performance status score of 0. Less than 30% of both groups had received any prior anticancer therapy.

The study met its primary endpoint of objective response rate (ORR): 39% in the combination group compared with 18% in the ipilimumab monotherapy group had an ORR, for an odds ratio (OR) of 2.9 (95% CI, 1.5–5.5; P = .002). Thirteen patients receiving talimogene laherparepvec had a complete response, compared with seven receiving ipilimumab alone. The disease control rate was 58% with the combination, and 42% with monotherapy.

Among patients with BRAF wild-type melanoma, the ORR was 42% with the combination, and 10% with ipilimumab alone, for an OR of 6.5 (95% CI, 2.4–17.4; P < .001). In BRAF-mutant tumors, the ORR was 34% and 32%, respectively, for an OR of 1.1 (95% CI, 0.4–3.0; P = 1.0).

The median time to response was 5.8 months with talimogene laherparepvec and ipilimumab, and it was not estimable with ipilimumab monotherapy. The median duration of response was not reached in either group. The median progression-free survival was 8.2 months with the combination and 6.4 months with monotherapy, for a hazard ratio (HR) of 0.83 (95% CI, 0.56–1.23; P = .35). The HR for overall survival was also not different, at 0.80 (95% CI, 0.44–1.46).

Grade 3 or higher adverse events occurred in 45% of combination therapy patients and in 35% of monotherapy patients. The most frequent adverse events were similar to those seen in other trials of these agents; three patients in the combination group had fatal adverse events, including myocardial infarction in one patient and two with disease progression; none were considered treatment related.

“The combination seems to have greater efficacy…without additional safety concerns vs ipilimumab alone in patients with unresected stages IIIB to IV melanoma,” the authors concluded. “The combination of talimogene laherparepvec and a checkpoint inhibitor may have significant clinical utility in treatment of advanced melanoma.”

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