Durvalumab
Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. A multicenter, open-label, phase 1 trial presented at the 2015 ASCO Annual Meeting showed that the immunotherapy can be combined with trametinib with or without dabrafenib for patients with BRAF-mutant and BRAF wild-type melanoma.6
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For the study, 50 patients with stage 3C or 4 melanoma were assigned to receive durvalumab 3 or 10 mg/kg intravenously every 2 weeks in combination with dabrafenib 150 mg orally twice daily plus trametinib 2 mg orally twice daily, or trametinib alone. Patients could also receive sequential trametinib followed by durvalumab 10 mg/kg.
Results showed that 6 of the 6 patients receiving the 3-drug combination with durvalumab at 3 mg/kg achieved a complete or partial response. Ten of the 15 patients receiving all 3 drugs with durvalumab at 10 mg/kg achieved a response. The researchers reported that most responses were ongoing.
The most common treatment-related adverse events were pyrexia, fatigue, diarrhea, rash, and vomiting.
“The data presented at the 2015 ASCO Annual Meeting were not spectacular, but long-term data are more important,” Dr Sullivan said. “Just the fact that this combination is doable is exciting.”
Eltrapuldencel-T
Eltrapuldencel-T is a novel dendritic cell-based vaccine that consists of autologous dendritic cells loaded with antigens from irradiated tumor cells derived from autologous melanoma cell lines, and suspended in granulocyte macrophage colony-stimulating factor.7
A phase 2 trial evaluating the activity and tolerability of the immunotherapy in 42 patients with stage 4 and recurrent stage 3 melanoma showed a 5-year survival rate of 50% with the vaccine. Toxicities associated with the vaccine were minimal.
Eltrapuldencel-T is being studied in the double-blind, placebo-controlled, phase 3 INTUS trial. For this study, researchers enrolled 250 patients with stage 4 or recurrent stage 3 melanoma and at least 1 lesion amenable to surgical resection.
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Participants were randomly assigned 2:1 to receive either eltrapuldencel-T or autologous mononuclear cells after undergoing leukapheresis to obtain mononuclear cells for each treatment arm. Patients in both arms will receive injections weekly for 3 weeks, and then monthly for 5 months.
The primary endpoint is overall survival, and final data collection for that outcome measure is estimated to be completed in January 2017.
