TY - JOUR
T1 - Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma
AU - Gibney, Geoffrey T.
AU - Kudchadkar, Ragini R.
AU - DeConti, Ronald C.
AU - Thebeau, Melissa S.
AU - Czupryn, Maria P.
AU - Tetteh, Leticia
AU - Eysmans, Cabell
AU - Richards, Allison
AU - Schell, Michael J.
AU - Fisher, Kate J.
AU - Horak, Christine E.
AU - Inzunza, H. David
AU - Yu, Bin
AU - Martinez, Alberto J.
AU - Younos, Ibrahim
AU - Weber, Jeffrey S.
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/2/15
Y1 - 2015/2/15
N2 - Purpose: The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. Experimental Design: 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. Results: 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. MTD was not reached. Most common related adverse events (>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 RFS was 47.1 months; median OS was not reached. Increases in CTLA-4 +/CD4+, CD25+Treg/CD4 +, and tetramer specific CD8 + T-cell populations were observed with treatment (P < 0.05). Trends for lower baselinemyeloid-derived suppressor cell and CD25 +Treg/CD4+ populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions: Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. Clin Cancer Res; 21(4); 712-20.
AB - Purpose: The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. Experimental Design: 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. Results: 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. MTD was not reached. Most common related adverse events (>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 RFS was 47.1 months; median OS was not reached. Increases in CTLA-4 +/CD4+, CD25+Treg/CD4 +, and tetramer specific CD8 + T-cell populations were observed with treatment (P < 0.05). Trends for lower baselinemyeloid-derived suppressor cell and CD25 +Treg/CD4+ populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions: Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. Clin Cancer Res; 21(4); 712-20.
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U2 - 10.1158/1078-0432.CCR-14-2468
DO - 10.1158/1078-0432.CCR-14-2468
M3 - Article
C2 - 25524312
AN - SCOPUS:84923166043
SN - 1078-0432
VL - 21
SP - 712
EP - 720
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -