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Clin Cancer Res. 2015 Feb 15;21(4):712-20. doi: 10.1158/1078-0432.CCR-14-2468. Epub 2014 Dec 18.

Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.

Author information

1
Department of Cutaneous Oncology and Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida. Department of Oncologic Sciences, University of South Florida, Tampa, Florida. geoffrey.gibney@moffitt.org.
2
Division of Oncology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
3
Department of Cutaneous Oncology and Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida. Department of Oncologic Sciences, University of South Florida, Tampa, Florida.
4
Department of Cutaneous Oncology and Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.
5
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
6
Bristol-Myers Squibb, Early Clinical and Translational Research, Princeton, New Jersey.
7
Department of Clinical Pharmacology, College of Medicine, Minufiya University, Minufiya, Egypt. Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.

Abstract

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 baseline myeloid-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.

PMID:
25524312
PMCID:
PMC4620684
DOI:
10.1158/1078-0432.CCR-14-2468
[Indexed for MEDLINE]
Free PMC Article

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