{"entity":{"id":"signatera","kind":"drug","name":"Signatera","aka":[],"tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA.","summary":"Signatera is Natera's tumour-informed MRD test and tracks 16 patient-specific variants. Medicare-covered in colorectal, breast, bladder, lung, ovarian, and immunotherapy monitoring. Used in interventional trials (CIRCULATE-US, ZEST in TNBC with niraparib, negative for feasibility reasons; IMvigor011 used Signatera to select ctDNA+ bladder patients for atezolizumab, leading to the first ctDNA-based approval in 2026).","status":"established","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04660344 (IMvigor011)","url":"https://clinicaltrials.gov/study/NCT04660344"}],"tags":[],"related":[],"cancers":["colorectal","urothelial","tnbc","nsclc","pancreatic"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":[],"companies":["natera"],"institutions":[],"pathways":[],"terms":[],"trials":["imvigor011","dynamic-iii","altair"],"people":[],"bottlenecks":[],"keyPapers":["paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021","paper-lee-ctdna-adjuvant-benefit-localized-pancreatic-ann-oncol-2019","paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019","paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019","paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022","paper-galaxy-signatera-nat-med-2023"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma: tumour-informed residual disease testing after resection is a research readout here; the published pancreatic series used bespoke KRAS droplet PCR or SafeSeqS rather than a commercial assay, and found every ctDNA-positive patient recurred (Lee 2019, Groot 2019).","Colorectal cancer: this is the disease with the deepest tumour-informed residual disease evidence. Week-4 positivity carried a recurrence hazard ratio of 10 in 1,039 prospectively followed patients (Kotani 2023), and serial testing separates patients who clear during adjuvant chemotherapy, who do not relapse, from those who do not (Henriksen 2022). No approval turns on the result; the randomised evidence is for de-escalation in stage II (DYNAMIC), not escalation."],"modality":"Tumour-informed ctDNA MRD test","mechanism":"WES of tumour → bespoke 16-plex PCR/NGS assay on plasma at very high depth.","approvals":[],"mechanismSteps":["Tumour tissue and normal DNA are sequenced (whole exome)","16 patient-specific clonal variants are chosen","A bespoke multiplex PCR assay is built","Plasma is tested at high depth at each visit","Detection of ≥2 variants calls ctDNA positive, months before imaging"],"toxicity":[],"access":[{"country":"US","listPrice":"~$3,500 per test (Medicare rate, approximate)","reimbursement":"Medicare covers colorectal (stage II-III and IV), muscle-invasive bladder, breast (neoadjuvant/adjuvant), ovarian, NSCLC and pan-cancer immunotherapy monitoring under MolDX; commercial coverage growing","source":"https://www.natera.com/oncology/signatera-advanced-cancer-detection/","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2019-05","type":"designation","region":"US","note":"FDA Breakthrough Device designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-03","type":"approval","region":"US","note":"Medicare coverage (MolDX) for stage II-III colorectal cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2021-10","type":"approval","region":"US","note":"Medicare coverage for immunotherapy response monitoring, pan-cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-Q2","type":"label-change","region":"US","note":"Used to select ctDNA-positive patients in the first ctDNA-guided drug approval (IMvigor011, atezolizumab)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/signatera/","neighbours":{"cancer":[{"id":"advanced-small-bowel-adenocarcinoma","kind":"cancer","name":"Advanced and metastatic small bowel adenocarcinoma","route":"/cancers/advanced-small-bowel-adenocarcinoma/"},{"id":"ampullary","kind":"cancer","name":"Ampullary cancer (ampulla of Vater)","route":"/cancers/ampullary/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"localised-small-bowel-adenocarcinoma","kind":"cancer","name":"Localised small bowel adenocarcinoma (stage I to III, resected)","route":"/cancers/localised-small-bowel-adenocarcinoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"},{"id":"small-bowel","kind":"cancer","name":"Small intestine cancer (small bowel adenocarcinoma)","route":"/cancers/small-bowel/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cea-surveillance-colorectal","kind":"technology","name":"CEA surveillance after colorectal cancer surgery","route":"/technologies/cea-surveillance-colorectal/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"company":[{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"trial":[{"id":"altair","kind":"trial","name":"ALTAIR","route":"/trials/altair/"},{"id":"bespoke-crc","kind":"trial","name":"BESPOKE CRC","route":"/trials/bespoke-crc/"},{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/"},{"id":"circulate-us","kind":"trial","name":"CIRCULATE-US","route":"/trials/circulate-us/"},{"id":"dynamic-iii","kind":"trial","name":"DYNAMIC-III","route":"/trials/dynamic-iii/"},{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/"}],"paper":[{"id":"paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019","kind":"paper","name":"Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer","route":"/key-papers/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019/"},{"id":"paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","kind":"paper","name":"Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer","route":"/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/"},{"id":"paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019","kind":"paper","name":"Circulating tumor DNA as a clinical test in resected pancreatic cancer","route":"/key-papers/paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019/"},{"id":"paper-lee-ctdna-adjuvant-benefit-localized-pancreatic-ann-oncol-2019","kind":"paper","name":"Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer","route":"/key-papers/paper-lee-ctdna-adjuvant-benefit-localized-pancreatic-ann-oncol-2019/"},{"id":"paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021","kind":"paper","name":"Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival","route":"/key-papers/paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021/"},{"id":"paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022","kind":"paper","name":"Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences","route":"/key-papers/paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022/"},{"id":"paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025","kind":"paper","name":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection","route":"/key-papers/paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025/"},{"id":"paper-dynamic-nejm-2022","kind":"paper","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","route":"/key-papers/paper-dynamic-nejm-2022/"},{"id":"paper-galaxy-signatera-nat-med-2023","kind":"paper","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","route":"/key-papers/paper-galaxy-signatera-nat-med-2023/"},{"id":"paper-imvigor011-nejm-2025","kind":"paper","name":"IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery","route":"/key-papers/paper-imvigor011-nejm-2025/"},{"id":"paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026","kind":"paper","name":"Real-world analysis of ctDNA and other biomarkers in patients with curatively resected stage I-III biliary tract cancer","route":"/key-papers/paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026/"}],"idea":[{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/"},{"id":"idea-fund-biomarker-validation-fund","kind":"idea","name":"A fund for prospective validation of academic biomarkers and companion diagnostics","route":"/ideas/idea-fund-biomarker-validation-fund/"},{"id":"idea-moon-mrd-weather-service","kind":"idea","name":"A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled","route":"/ideas/idea-moon-mrd-weather-service/"},{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/"},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/"},{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"},{"id":"idea-ctdna-escalation-tnbc","kind":"idea","name":"ctDNA-triggered escalation in early TNBC","route":"/ideas/idea-ctdna-escalation-tnbc/"},{"id":"idea-tr2-ctdna-mrd-qualification","kind":"idea","name":"Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials","route":"/ideas/idea-tr2-ctdna-mrd-qualification/"},{"id":"idea-late-recurrence-interception","kind":"idea","name":"Intercepting late recurrence with ctDNA surveillance and oral SERDs","route":"/ideas/idea-late-recurrence-interception/"},{"id":"idea-crc-ctdna-de-escalation-beyond-stage-ii","kind":"idea","name":"Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps","route":"/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-roadmap/"},{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"pairing":[{"id":"ctdna-mrd-to-adjuvant","kind":"pairing","name":"ctDNA MRD → adjuvant therapy decision","route":"/pairings/ctdna-mrd-to-adjuvant/"}],"person":[{"id":"jeanne-tie","kind":"person","name":"Jeanne Tie","route":"/people/jeanne-tie/"},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"term":[{"id":"biomarker-stratified-design","kind":"term","name":"Enrichment and biomarker-stratified designs","route":"/terms/biomarker-stratified-design/"},{"id":"fda-ldt-rule","kind":"term","name":"FDA laboratory-developed test (LDT) rule","route":"/terms/fda-ldt-rule/"},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/"}],"pathway":[{"id":"drug-tolerant-persisters","kind":"pathway","name":"Drug-tolerant persister cells","route":"/pathways/drug-tolerant-persisters/"},{"id":"intravasation-ctc-survival","kind":"pathway","name":"Intravasation & circulating tumour cells","route":"/pathways/intravasation-ctc-survival/"},{"id":"pre-metastatic-niche","kind":"pathway","name":"The pre-metastatic niche","route":"/pathways/pre-metastatic-niche/"}],"drug":[{"id":"guardant-reveal","kind":"drug","name":"Guardant Reveal","route":"/drugs/guardant-reveal/"},{"id":"oncodetect","kind":"drug","name":"Oncodetect","route":"/drugs/oncodetect/"},{"id":"radar-mrd","kind":"drug","name":"RaDaR","route":"/drugs/radar-mrd/"}],"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"}]}}