The anti-programmed death-1 ( PD-1 ) antibody Nivolumab ( Opdivo ) has clinical activity in patients with metastatic melanoma.
Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients.
HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received Nivolumab ( 1 mg/kg, 3 mg/kg, or 10 mg/kg i.v. ) with a multi-peptide vaccine ( gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG ) every 2 weeks for 12 doses followed by Nivolumab maintenance every 12 weeks for 8 doses.
Primary objective was safety and determination of a maximum tolerated dose ( MTD ). Secondary objectives included relapse-free survival ( RFS ), overall survival ( OS ), and immunologic correlative studies.
Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease.
Median follow-up was 32.1 months.
Maximum tolerated dose was not reached.
Most common related adverse events ( more than 40% ) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias.
Five related grade 3 adverse events [ hypokalemia ( 1 ), rash ( 1 ), enteritis ( 1 ), and colitis ( 2 ) ] were observed.
Ten of 33 patients relapsed.
Estimated median relapse-free survival was 47.1 months; median overall survival was not reached.
Increases in CTLA-4(+)/CD4(+), CD25(+)Treg/CD4(+), and tetramer specific CD8(+) T-cell populations were observed with treatment ( P less than 0.05 ).
Trends for lower baseline myeloid-derived suppressor cell and CD25(+)Treg/CD4(+) populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with relapse-free survival.
In conclusion, Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. ( Xagena )
Gibney GT et al, Clin Cancer Res 2015;21:712-720