Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma.
Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in Ipilimumab-refractory and -naive melanoma.
In a phase I study, 90 patients with unresectable stage III or IV melanoma who were Ipilimumab naive and had experienced progression after at least one prior therapy ( cohorts 1 to 3, 34 patients ) or experienced progression after prior Ipilimumab ( cohorts 4 to 6, 56 patients ) received Nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine.
Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both Ipilimumab-refractory and -naive patients was 25%.
Median duration of response was not reached at a median of 8.1 months of follow-up.
High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease.
At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression.
PD-L1 tumor staining was associated with responses to Nivolumab, but negative staining did not rule out a response.
Patients who experienced progression after Nivolumab could respond to Ipilimumab ( Yervoy ).
In conclusion, in patients with Ipilimumab-refractory or -naive melanoma, Nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks.
Responses to Nivolumab in Ipilimumab-refractory patients or to Ipilimumab in Nivolumab-refractory patients support combination or sequencing of Nivolumab and Ipilimumab. ( Xagena )
Weber JS et al, J Clin Oncol 2013; 31: 4311-4318