Skip navigation

Know earlier if ICI treatment is working

During treatment with immune-checkpoint inhibitors (ICI) for advanced or metastatic cancers, you want answers to critical questions as soon as possible. Is the treatment working? Is the tumor truly progressing? Should you change or restart treatment? Covered by Medicare for pan-cancer immunotherapy monitoring, including all eligible immune checkpoint inhibitors, Signatera is a personalized tumor-informed assay for ultrasensitive detection of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) to assess treatment response in conjunction with standard imaging.


The challenges of ICI treatment.
The power of ctDNA.

Despite dramatic improvements in metastatic cancer care using antibodies that block the immune checkpoint proteins CTLA-4, PD-1, or PD-L1, the reality is ICI-based treatments don’t work for everyone:

  • About 43.5% of cancer patients are eligible for ICI treatment.1,2
  • Less than 20% of eligible patients will derive sustained response or clinical benefit to ICIs.1,2

Early and ultrasensitive monitoring of tumor progression is key to improving patient outcomes in the immuno-oncology (IO) setting. Existing methods, including CT scans and serum protein biomarkers, are unreliable in this regard.

Signatera enables highly sensitive cancer monitoring by tracking the patient’s unique tumor mutational signature in circulating tumor DNA (ctDNA). This tumor-informed approach also makes it possible to evaluate IO treatment response much earlier than CT scans and serum protein biomarkers.

Why is Signatera important?

Signatera can be used alongside imaging tests to better assess response to immunotherapy and help determine whether the tumor is progressing or not.

Signatera at a Glance

Each Signatera test is personalized and tumor-informed. Whole exome sequencing of the tumor tissue allows a bespoke Signatera assay to be created, which detects ctDNA from only clonal mutations. Tracking ctDNA unique to the patient’s clonal mutation signature is key to enabling a highly sensitive and specific test with a low limit of detection, down to 0.01% VAF.3, 4, 5, 6

  • Personalized, tumor-informed assay
  • Tumor-specific, clonal mutations identified by whole exome sequencing of patient’s tumor tissue to eliminate germline and CHIP mutations
  • Ultrasensitive ctDNA detection with multiplex PCR technology
  • Highly sensitive and specific with a low limit of detection
  • Optimized for longitudinal monitoring
  • Measures only clonal mutations, which correlates with tumor burden

Personalized, tumor-informed assay

One-time, primary tissue sample and matched normal tissue is required for whole exome sequencing and personalized test design.

Ultrasensitive ctDNA detection

Signatera detects ctDNA of somatic and truncal variants to optimize sensitivity. Tumor-informed method enables filtering of CHIP mutations to decrease false positive rates.

Optimized for longitudinal monitoring

Once the patient’s personalized test has been designed, only a blood sample is needed each subsequent time Signatera is ordered.

How to use Signatera in your practice

Is the treatment working? Read more about a stage IV non-small cell lung cancer (NSCLC) patient who experienced early tumor progression during first-line immunotherapy treatment cancer color icon Download
Is the tumor truly progressing? Read more about a stage IV melanoma patient with an indeterminate imaging result during immunotherapy treatment functional testing icon Download
Is there a need to change or reinitiate treatment? Read more about a stage IV non-small cell lung cancer (NSCLC) patient who was able to discontinue immunotherapy treatment after a prolonged, durable, complete response functional testing icon Download

INSPIRE Trial: Validating ctDNA as an early biomarker of ICI treatment response

Signatera was evaluated in the INSPIRE trial, a randomized, prospective study in patients with advanced or metastatic solid malignancies receiving pembrolizumab treatment.7

  • 98% of patients had detectable ctDNA at baseline
  • An increase in ctDNA levels from baseline at week 6 strongly predicted disease progression and non-response to pembrolizumab
  • Achieving ctDNA clearance at any time during treatment correlated with durable OS

Combined with imaging tools, Signatera ctDNA analysis provides several clinical benefits:

  • Assess therapeutic benefit of ICIs in real time
  • Rule-out pseudo-progression early
  • Assists in interpretations of ambiguous imaging results
  • Increase confidence in decisions to continue, switch, or reinitiate ICI
  • Improve the management of patients with durable, radiographically stable disease

Overall survival was 100% in patients who experienced ctDNA clearance for at least one on-treatment time point

Positive Result

BESPOKE study of ctDNA guided immunotherapy (IO)

The BESPOKE IO clinical study will collect data and blood samples from patients with advanced or metastatic solid tumors who will receive standard of care ICIs. The study will determine how routine Signatera testing impacts treatment decisions and early detection of disease progression when integrated as part of routine assessment of tumor response.


Natera and its collaborators will collect clinical utility and outcome data for two years from patient enrollment. This data will help better understand how Signatera ctDNA test results correlate to responses to ICIs and how Signatera can help physicians and patients in treatment planning.

BESPOKE study of ctDNA guided immunotherapy (IO)

Learn more about immunotherapy monitoring

Dr. Luis Raez, Medical Director and Chief Scientific Officer of Memorial Cancer Institute in Florida, discusses ctDNA testing and how the personalized, tumor-informed assay Signatera can be used for immunotherapy response monitoring.

Check out our FAQs to learn more about Signatera

Questions about Signatera? Submit your inquiries here.


1Haslam A, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Network Open. 2019;2(5):e192535-e192535.

2Haslam A, Gill J, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for Immune Checkpoint Inhibitor Drugs. JAMA Netw Open. 2020;3(3):e200423. doi:10.1001/jamanetworkopen.2020.0423

3Reinert T, Henriksen TV, Christensen E, et al. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stage I to III Colorectal Cancer. JAMA Oncology. 2019;5(8):1124-1131.

4Coombes C, Page K, Salari R, et al. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clinical Cancer Research. 2019;25(14):4255-4263.

5Abbosh C, Birkbak N, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017,545:446–451

6Christensen E, Birkenkamp-Demtröder K, Sethi H, et al. Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients with Urothelial Bladder Carcinoma. 2019; 37(18):1547-1557.

7Bratman SV, Yang SYC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2020;1:873–881.