Tawbi HA, et al. - In this open-label, multicenter, phase 2 study, researchers tested the safety as well as the efficacy of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. They found that nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases.

Methods

• Study participants were patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects.
• The rate of intracranial clinical benefit was the primary end point, characterized as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.

Results

• The rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2% among 94 patients with a median follow-up of 14.0 months.
• Findings revealed that the rate of extracranial clinical benefit was 56% (95% CI, 46 to 67).
• It was noted that treatment-related grade 3 or 4 adverse events were reported in 55% of subjects, including events involving the central nervous system in 7%.
• From immune-related myocarditis, one patient died.
• In patients with melanoma who do not have brain metastases, the safety profile of the regimen was similar to that reported.