Skip to main content
Back to Resources

Immunotherapy Biomarkers

Overview

We’re helping to uncover immunotherapy options for more patients

癌症免疫疗法通过利用我们自己的免疫系统的力量来治疗癌症;然而,并非所有癌症免疫治疗所有患者都适用。

常见的免疫疗法称为检查点抑制剂治疗通常仅引发了仅限的整体反应率(ORR)20-40%金博宝188亚洲体育app适用于固体肿瘤的患者。1,2,3预测谁最有可能响应癌症免疫治疗的能力可以节省大量成本和宝贵的时间。

The standard of care immunotherapy-related biomarker, programmed death-ligand 1 (PD-L1), may not provide a complete picture of potential candidates for immunotherapy.⁴ We need to look beyond PD-L1 to other clinically relevant genomic signatures that can help stratify patients such as tumor mutational burden (TMB), a quantitative measurement linked to neoantigen expression, and microsatellite instability (MSI) status, which indicates deficient mismatch repair (dMMR).5

博188金宝基金会医学提供了综合基因组分析试验的组合,可以为您的晚期患者提供TMB,MSI,*和PD-L1结果。

Help Identify More Eligible Patients

TMB和MSI是添加到标准PD-L1测试的重要基因组特征,因为它们可能有助于识别更多患者,该患者可以成为一种选择。

All three populations, patients with elevated TMB, high MSI, and positive PD-L1-status, have independently demonstrated improved response rate and prolonged progression-free survival on immunotherapy.7,8,9.然而,有一组患者只针对这三种生物标志物中的一种进行阳性。

14% of patients who test negative for PD-L1 by IHC have high MSI or elevated TMB, which may help inform immunotherapy decisions.6

14% of patients who test negative for PD-L1 by IHC have high MSI or elevated TMB, which may help inform immunotherapy decisions

博188金宝基础医学是您对癌症免疫疗法信息的资源

综合基因组分析与底座®CDX,底座®LiquidCDX和底座®血清可以向相关的癌症相关基因提供见解,并测量可能与之相关的TMB,MSI和PD-L1的其他基因组特征和临床生物标志物用免疫疗法。

Our tests can help physicians identify patients who may be more likely to benefit from immunotherapy by providing all relevant genomic signatures from a single vendor.

订购测试

Relevant Genomic Signatures

Tumor Mutational Burden (TMB)

TMB is a genomic signature that quantifies the frequency of somatic mutations in a patient’s tumor tissue or in circulating tumor DNA in blood. FoundationOne CDx, FoundationOne Liquid CDx,* and FoundationOne Heme report TMB scores. As TMB is a quantitative genomic signature, current clinical trials are assessing therapeutic response at various cut-off levels in different tumor types.

Elevated TMB correlates with higher neoantigen expression, which helps the immune system recognize tumors.5它已被检测到众多肿瘤类型,并与免疫疗法患者的患者的响应率和无延长的进展生存有关。金博宝188亚洲体育app10、11TMB扩大了可将候选人视为免疫疗法的患者患者的患者。10、12

博188金宝基础医学已经建立了与WES的综合基因组分析试验的一致性,并证明了TMB的临床效用,以有效地预测超过1,300名患者的600多名不同肿瘤类型的600多名患者的免疫治疗响应和存活。5,10,12

Scatter plot showing concordance of Foundation Medicine comprehensive genomic profiling tests with whole exome sequencing.

底座CDX,底座液体CDX,*和底座HEME在没有任何其他样本要求,测试申请表或成本的情况下提供TMB分数。

*群体液体CDX报告血液肿瘤突变负担(BTMB)status.13

Relevant Genomic Signatures

Microsatellite Instability (MSI)

MSI是一种基因组特征,是缺陷不匹配修复(DMMR)的签名,其导致异常高的遗传突变频率。14MSI-high status correlates with higher neoantigen expression which helps the immune system recognize tumors. Identification of MSI-high status is part of an FDA-approved indication for pembrolizumab, an immunotherapy drug that has expanded its approval across all solid tumor types in MSI-high patients when previous therapies have failed.15High MSI levels have been detected in more than 20 types of solid tumors, thus underlining the importance of testing all patients for this key genomic signature.5,16

博188金宝基础医学’s hybrid-capture, next-generation sequencing (NGS) methodology has high sensitivity and specificity for clinical MSI-high testing across tumor types.17

Longtail plot showing Microsatellite Instability High prevalence across a variety of cancer types

FoundationOne CDx, FoundationOne Liquid CDx,*and FoundationOne Heme provide MSI status on all reports without any additional tissue, test requisition form, or cost.

*在底座液体CDX上,将报告MSI状态,用于确定具有高微卫星不稳定性的样品。 

Relevant Genomic Signatures

箴grammed Death Ligand-1 (PD-L1)

PD-L1是一种与免疫系统抑制强烈相关的蛋白质生物标志物。18阳性PD-L1免疫组织化学(IHC)可以表明患者更有可能反应免疫疗法。然而,这种生物标志物的可变性突出了需要额外的工具来预测可用于免疫疗法的候选者。4

Beyond PD-L1, TMB and MSI can help you identify and treat more patients eligible for immunotherapy. By combining PD-L1, TMB, and MSI testing, you can be more confident that you are considering all viable treatment options for your patients.

与重叠圈子的图表显示有人们对PD-L1进行负面测试,但是MSI高或升高的TMB

PD-L1可与底座CDX,底座液体CDX和底座血管订购,以及相同的测试申请表。PD-L1测试只需要四个额外的未染色幻灯片,并为我们的标准周转时间添加了额外的等待时间。PD-L1测试的评分和克隆利用率基于FDA批准的指示,learn more here

下载IHC标本说明

概括

Biomarker Summary

博188金宝基础医学的产品组合通过IHC的全面基因组分析和PD-L1表达提供了可靠和准确的TMB和MSI测量。利用我们的测试全面帮助您为患者提供免疫疗法治疗选择。

订购测试

Tumor Mutational Burden (TMB)

Definition

TMB is a genomic signature that quantifies the frequency of somatic mutations in a patient’s tumor or in circulating tumor DNA in blood. Increasing TMB correlates with increased numbers of neoantigens, which helps the immune system recognize tumors.

At Foundation Medicine

*群体液体CDX报告血液肿瘤突变负担(BTMB)

报告为

  • Integer score

  • Therapies, trials and content (in the professional services section of Foundation Medicine reports) will be reported using disease- and therapy-specific, score-based cutoffs based on existing clinical data, which may change over time as additional clinical data becomes available.

Microsatellite Instability (MSI)

Definition

MSI is a genomic signature of deficient mismatch repair (dMMR) — which results in an abnormally high frequency of genetic mutations. MSI-high status correlates with higher neoantigen expression, which helps the immune system recognize tumors.

At Foundation Medicine

*MSI status will be reported for samples determined to have high microsatellite instability.

报告为

FoundationOne CDx and
FoundationOne Heme
:

  • MSI-HIGH

  • MSS (microsatellite stable)

  • CBD (cannot be determined)

FoundationOne Liquid CDx:

  • MSI-HIGH

  • CBD (cannot be determined)

箴grammed Death Ligand-1 (PD-L1)

Definition

PD-L1是一种蛋白质生物标志物,其表达预测对多种肿瘤类型的免疫疗法的反应,如许多临床试验所示。

At Foundation Medicine

*需要血液和组织标本进行底座液体CDX和PD-L1测试

报告为

IHC评分的类型取决于肿瘤类型。评分和克隆利用是基于FDA-approved indications

  • Tumor proportion score (TPS)

  • 合并阳性分数(CPS)

  • 肿瘤细胞(TC)得分(%)

  • 肿瘤浸润免疫细胞(IC)得分(%)

参考

1. Márquez-Rodas et al. Immune checkpoint inhibitors: therapeutic advances in melanoma. Ann Transl Med. 2015;3(18):267.

2. Wolchok et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-33.

3. Lipson et al. Antagonists of PD-1and PD-L1 in Cancer Treatment. Seminars in Oncology. 2015;42(4):587-600.

4. Kerr KM, Hirsch FR. Programmed Death Ligand-1 Immunohistochemistry: Friend Or Foe? Arch Pathol Lab Med. 2016;140:326–31. doi: 10.5858/arpa.2015-0522-SA.

Chalmers Zr等。分析100,000人癌症基因组揭示肿瘤突变负担的景观。Genome Med。2017; 9:34。DOI:10.1186 / s13073-017-0424-2。

6. Data based on Foundation Medicine experience as of June 2017.

7. Samstein RM. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics 2019;51:202-206.

8. Stenger M. Pembrolizumab in MSI-H or dMMR Solid Tumors: ‘First Tissue/Site-Agnostic’ Approval by FDA. The ASCO Post [Internet]. 2018 Feb 10 [cited 2019 Jan 2]. Available from:www.ascopost.com/issues/february-10-2018/pembrolizumab-in-msi-h-or-dmmr-solid-tumors-first-tissuesite-agnostic-approval-by-fda/

9. Center for Drug Evaluation and Research. (2019, February 06). Approved Drugs - Hematology/Oncology (Cancer) Approvals & Safety Notifications. Retrieved February 07, 2019, fromwww.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm

10. Goodman AM, et al. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017;16(11):2598-608. doi: 10.1158/1535-7163.MCT-17-0386.

11. Carbone D, et al. First-line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376:2415-26. doi: 10.1056/NEJMoa1613493.

12. Internal Data on File.

13. Gandara等。Nat Med。2018年9月24日(9):1441-1448。DOI:10.1038 / S41591-018-0134-3。EPUB 2018 8月6日。

14. Kim TM, Laird PW, Park PJ. The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes. Cell. 2013;155(4):858-68. doi: 10.1016/j.cell.2013.10.015.

15. Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2014.

16. Cortes-Ciriano I等。多种癌症微卫星不稳定性的分子肖像。自然交流。2017; 8:15180。

17. Hall MJ,等人。使用综合基因组专业(CGP)评估微卫星不稳定性(MSI)状态11,573种类的实体肿瘤。海报会议:2016年ASCO年会;2016年6月3日至7日;芝加哥,IL。

18. Xu-Monette ZY, et al. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response? Front Immunol. 2017;8:1597. doi:10.3389/fimmu.2017.01597.

开发了底座血红素及其基础药物的性能特征。博188金宝它尚未得到美国食品和药物管理局的清算或批准。有关该实验室开发测试的更多信息,请参阅技术规格foundationmedicine.com/f1h

我们在这里提供帮助

问题?我们的客户服务团队随时为您提供帮助。

联系我们

重要的安全信息

Select

FoundationOne CDx

FoundationOne®CDx is a qualitative next-generation sequencing basedin vitrodiagnostic test for advanced cancer patients with solid tumors and is for prescription use only. The test analyzes 324 genes as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For the complete label, including companion diagnostic indications and important risk information, please visitwww.F1CDxLabel.com。 

FoundationOne Liquid CDx

Bodaine®Liquidcdx仅用于处方使用,是基于定性的下一代测序in vitrodiagnostic test for advanced cancer patients with solid tumors. The test analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes and as a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visitwww.f1lcdxlabel.com.