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Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma - CM066-WES

Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001004567 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00004186659 fastq.gz 4.8 GB
EGAF00004186660 fastq.gz 4.9 GB
EGAF00004186661 fastq.gz 4.0 GB
EGAF00004186662 fastq.gz 4.2 GB
EGAF00004186663 fastq.gz 3.6 GB
EGAF00004186664 fastq.gz 3.8 GB
EGAF00004186665 fastq.gz 3.4 GB
EGAF00004186666 fastq.gz 3.6 GB
EGAF00004186667 fastq.gz 3.2 GB
EGAF00004186668 fastq.gz 3.3 GB
EGAF00004186669 fastq.gz 3.5 GB
EGAF00004186670 fastq.gz 3.6 GB
EGAF00004186671 fastq.gz 3.6 GB
EGAF00004186672 fastq.gz 3.7 GB
EGAF00004186673 fastq.gz 3.8 GB
EGAF00004186674 fastq.gz 3.9 GB
EGAF00004186675 fastq.gz 3.3 GB
EGAF00004186676 fastq.gz 3.3 GB
EGAF00004186677 fastq.gz 4.2 GB
EGAF00004186678 fastq.gz 4.3 GB
EGAF00004186679 fastq.gz 4.3 GB
EGAF00004186680 fastq.gz 4.6 GB
EGAF00004186681 fastq.gz 4.4 GB
EGAF00004186682 fastq.gz 4.3 GB
EGAF00004186683 fastq.gz 3.2 GB
EGAF00004186684 fastq.gz 3.4 GB
EGAF00004186685 fastq.gz 3.2 GB
EGAF00004186686 fastq.gz 3.3 GB
EGAF00004186687 fastq.gz 4.0 GB
EGAF00004186688 fastq.gz 4.0 GB
EGAF00004186689 fastq.gz 3.8 GB
EGAF00004186690 fastq.gz 3.8 GB
EGAF00004186691 fastq.gz 3.9 GB
EGAF00004186692 fastq.gz 4.1 GB
EGAF00004186693 fastq.gz 5.0 GB
EGAF00004186694 fastq.gz 4.8 GB
EGAF00004186695 fastq.gz 4.6 GB
EGAF00004186696 fastq.gz 4.7 GB
EGAF00004186697 fastq.gz 3.4 GB
EGAF00004186698 fastq.gz 3.5 GB
EGAF00004186699 fastq.gz 4.2 GB
EGAF00004186700 fastq.gz 4.3 GB
EGAF00004186701 fastq.gz 3.5 GB
EGAF00004186702 fastq.gz 3.7 GB
EGAF00004186703 fastq.gz 3.7 GB
EGAF00004186704 fastq.gz 3.9 GB
EGAF00004186705 fastq.gz 4.3 GB
EGAF00004186706 fastq.gz 4.5 GB
EGAF00004186707 fastq.gz 3.4 GB
EGAF00004186708 fastq.gz 3.6 GB
EGAF00004186709 fastq.gz 4.4 GB
EGAF00004186710 fastq.gz 4.5 GB
EGAF00004186711 fastq.gz 3.4 GB
EGAF00004186712 fastq.gz 3.5 GB
EGAF00004186713 fastq.gz 4.7 GB
EGAF00004186714 fastq.gz 4.8 GB
EGAF00004186715 fastq.gz 4.2 GB
EGAF00004186716 fastq.gz 4.4 GB
EGAF00004186717 fastq.gz 4.4 GB
EGAF00004186718 fastq.gz 4.6 GB
EGAF00004186719 fastq.gz 3.1 GB
EGAF00004186720 fastq.gz 3.4 GB
EGAF00004186721 fastq.gz 4.4 GB
EGAF00004186722 fastq.gz 4.1 GB
64 Files (253.3 GB)