Oncolytic virus boosts ipilimumab response in advanced melanoma
medwireNews: Combining the oncolytic virus talimogene laherparepvec with the immune checkpoint inhibitor ipilimumab significantly improves treatment response compared with ipilimumab alone in patients with advanced melanoma, phase II study data show.
The response to combined treatment occurred without additional safety concerns and was observed in patients with and without visceral disease, including in some uninjected lesions, Jason Chesney (University of Louisville, Kentucky, USA) and co-authors report in the Journal of Clinical Oncology.
They found that the 98 patients randomly assigned to receive treatment with talimogene laherparepvec plus ipilimumab had an objective response rate (ORR) of 39% during a median follow-up of 68 weeks. This was significantly higher than the ORR of 18% recorded among the 100 patients randomly assigned to use ipilimumab alone during a median 58 weeks of follow-up, and resulted in an odds ratio of 2.9 in favour of the combined treatment.
All study participants had unresectable stage IIIB to IV melanoma, with limited prior therapy, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression.
Patients in the combined treatment group received intralesional talimogene laherparepvec at a dose of 106 plaque-forming units/mL up to a maximum volume of 4 mL in week 1 and then at a dose of 108 plaque-forming units/mL (≤4.0 mL) every 2 weeks from week 4 onwards as well as intravenous ipilimumab 3 mg/kg every 3 weeks from week 6 onwards for up to four infusions. Patients receiving ipilimumab alone began their treatment in week 1.
The researchers found that the responses were not limited to injected lesions; 52% of patients in the combination arm and 23% of those in the ipilimumab arm experienced decreases in visceral lesion burden, while 57% and 56%, respectively, experienced a reduction in uninjected nonviseceral lesions.
However, they point out that the number of patients with uninjected nonviseceral lesions was smaller in the combination arm than in the control arm and say that the findings “indicate that the combination elicited a greater systemic antitumor response than could be achieved with either agent alone.”
The disease control rate was significantly higher with talimogene laherparepvec plus ipilimumab than with ipilimumab alone, at 58% versus 42%, and was higher in the combination arm across all subgroups, apart from patients with BRAF mutations, who also showed no significant benefit in ORR with combined therapy.
Median progression-free survival was longer in the combination arm than in the ipilimumab arm, at 8.2 versus 6.4 months, even though ipilimumab treatment started 5 weeks later in the combination arm, but the difference was not statistically significant.
Chesney and team did not observe any unexpected adverse events or an increase in the incidence or severity of such events, “suggesting that combination therapy is tolerable for patients with advanced melanoma,” they write.
The authors conclude: “The combination of talimogene laherparepvec and a checkpoint inhibitor may have significant clinical utility in treatment of advanced melanoma.”
By Laura Cowen
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