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Malignancies","nct":"NCT05786924","phase":"1/2","status":"recruiting"},{"id":"nct05503888","name":"Phase Ib/II Study of Almonertinib Combined With SHR-1701 in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer","nct":"NCT05503888","phase":"1/2","status":"planned"},{"id":"nct05358249","name":"Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation","nct":"NCT05358249","phase":"1/2","status":"active"},{"id":"nct04486833","name":"Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib","nct":"NCT04486833","phase":"1/2","status":"recruiting"},{"id":"nct07468071","name":"Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other","nct":"NCT07468071","phase":"1/2","status":"recruiting"},{"id":"nct06567015","name":"Study of FIH of STX-241 in Locally Advanced or Metastatic NSCLC Resistant to EGFR TKIs","nct":"NCT06567015","phase":"1/2","status":"recruiting"},{"id":"nct04956640","name":"Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)","nct":"NCT04956640","phase":"1/2","status":"active"},{"id":"nct07448116","name":"Study of MCLA-129 in Combination With Ensartinib in Patients With Advanced Solid Tumors.","nct":"NCT07448116","phase":"1/2","status":"recruiting"},{"id":"nct04930432","name":"Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors","nct":"NCT04930432","phase":"1/2","status":"recruiting"},{"id":"nct07079475","name":"Study of Oral EGFR Inhibitor DZD6008 Combined With Sunvozertinib in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN8)","nct":"NCT07079475","phase":"1/2","status":"recruiting"},{"id":"nct06445062","name":"Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors","nct":"NCT06445062","phase":"1/2","status":"recruiting"},{"id":"nct04585035","name":"Study to Evaluate D-1553 in Subjects With Solid Tumors","nct":"NCT04585035","phase":"1/2","status":"active"},{"id":"nct04665206","name":"Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors","nct":"NCT04665206","phase":"1/2","status":"recruiting"},{"id":"nct07204574","name":"The Phase 1b/IIa, Open-label, Dose Escalation and Dose Expansion to Evaluate Safety, Tolerability, and Preliminary Efficacy of the Combination of HCB101, Cetuxi","nct":"NCT07204574","phase":"1/2","status":"recruiting"},{"id":"nct07044908","name":"TQB2922 and TAS-102 Tablets for Injection With or Without Bevacizumab in Chemotherapy-failed RAS/BRAF Wild-type Advanced Colorectal Cancer","nct":"NCT07044908","phase":"1/2","status":"recruiting"},{"id":"chrysalis","name":"CHRYSALIS","nct":"NCT02609776","phase":"1","status":"active"},{"id":"nct05647122","name":"First in Human Study of AZD9592 in Solid Tumors","nct":"NCT05647122","phase":"1","status":"active"}],"pathways":["breast-cancer-signalling","choline-metabolism-in-cancer","chromosomal-instability","colorectal-cancer-signalling","drug-tolerant-persisters","glioma-signalling","lineage-plasticity-neuroendocrine","nsclc-signalling","prostate-cancer-signalling","ras-mapk","rtk-activation","resistance-routes-map"],"companies":["abbvie","amgen","aosaikang-pharmaceutical","arrivent","astellas","astrazeneca","betta","bicara-therapeutics","biocon","black-diamond-therapeutics","boehringer-ingelheim","bms","celldex","cimab","cspc","dizal","eli-lilly","engeneic","eurofarma","genmab","guardant-health","hanmi-pharmaceutical","hansoh-pharma","hummingbird-bioscience","hutchmed","imagene-ai","inivata","hengrui","johnson-johnson","lucence","merck","merus","novartis","oric-pharmaceuticals","pfizer","puma-biotechnology","qiagen","rakuten-medical","roche-genentech","sanofi","allist","henlius","junshi","sino-biopharm","spectrum-pharmaceuticals","systimmune","taiho-oncology","takeda","tempus","thermo-fisher"],"keyPapers":["paper-adaura-8-year-os-jto-2026","paper-flaura2-long-term-safety-lung-cancer-2026","paper-breakwater-nejm-2025","paper-erices-chilean-gallbladder-landscape-front-oncol-2025","paper-mariposa-nejm-2024","paper-lu-laura-osimertinib-stage-iii-nejm-2024","paper-codebreak-300-nejm-2023","paper-krystal-1-crc-yaeger-nejm-2023","paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","paper-paradigm-jama-2023","paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-adaura-nejm-2020","paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","paper-offin-rb1-tp53-transformation-risk-jto-2019","paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","paper-lenz-cms-calgb-swog-80405-jco-2019","paper-keynote-048-lancet-2019","paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","paper-flaura-nejm-2018","paper-archer-1050-os-jco-2018","paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","paper-lindeman-lung-molecular-testing-guideline-jto-2018","paper-lee-clonal-history-small-cell-transformation-jco-2017","paper-archer-1050-lancet-oncol-2017","paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017","paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017","paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","paper-tracerx-100-nejm-2017","paper-campbell-pan-lung-somatic-alterations-nat-genet-2016","paper-awad-met-exon-14-mutations-lung-jco-2016","paper-thress-nat-med","paper-tcga-lung-adenocarcinoma-nature-2014","paper-missiaglia-distal-proximal-colon-cancers-ann-oncol-2014","paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","paper-kris-lung-cancer-mutation-consortium-jama-2014","paper-li-gallbladder-exome-erbb-nat-genet-2014","paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-douillard-prime-panitumumab-ras-nejm-2013","paper-tcga-breast-molecular-portraits-nature-2012","paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","paper-lehmann-tnbc-subtypes-jci-2011","paper-lemmon-schlessinger-rtk-signalling-cell-2010","paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","paper-karapetis-kras-cetuximab-colorectal-nejm-2008","paper-soda-eml4-alk-fusion-nature-2007","paper-engelman-met-amplification-gefitinib-resistance-science-2007","paper-pao-egfr-t790m-acquired-resistance-plos-med-2005","paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-paez-egfr-mutations-gefitinib-science-2004","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"hotspots":[{"label":"Exon 19 deletions","position":746,"kind":"activating","frequency":"About 45% of EGFR-mutant NSCLC","drugs":["osimertinib","lazertinib","amivantamab","erlotinib","gefitinib","afatinib","dacomitinib"]},{"label":"L858R","position":858,"kind":"activating","frequency":"About 40% of EGFR-mutant NSCLC","drugs":["osimertinib","lazertinib","amivantamab","erlotinib","gefitinib","afatinib","dacomitinib"]},{"label":"G719X / S768I / L861Q","position":719,"kind":"activating","frequency":"About 10% of EGFR mutations (uncommon alleles)","drugs":["afatinib","osimertinib"]},{"label":"Exon 20 insertions","position":762,"kind":"activating","frequency":"About 4 to 10% of EGFR mutations","drugs":["amivantamab","sunvozertinib"]},{"label":"T790M","position":790,"kind":"resistance","frequency":"About 50 to 60% of progression on first- and second-generation TKIs","drugs":["osimertinib","lazertinib","amivantamab"]},{"label":"C797S","position":797,"kind":"resistance","frequency":"About 7 to 15% after first-line osimertinib","drugs":["amivantamab","izalontamab-brengitecan","patritumab-deruxtecan","datopotamab-deruxtecan"]}],"openQuestions":[{"id":"egfr-c797s-fourth-gen","question":"Which agent should follow osimertinib when C797S emerges: a fourth-generation TKI, amivantamab-based therapy, or an ADC that ignores genotype?","stage":"translational","actor":"industry","source":{"label":"FLAURA2, NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2306434"}},{"id":"egfr-first-line-intensity","question":"Which patients need intensified first-line therapy (osimertinib plus chemotherapy, or amivantamab plus lazertinib) and which are well served by osimertinib alone?","stage":"clinical","actor":"clinic","source":{"label":"MARIPOSA, NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2403614"}}],"assays":[{"id":"egfr-cobas-v2","name":"cobas EGFR Mutation Test v2","cutoff":"Mutation detected (qualitative); plasma negative result should be reflexed to tissue"},{"id":"egfr-therascreen","name":"therascreen EGFR RGQ PCR Kit","cutoff":"Mutation detected (qualitative)"},{"id":"kras-therascreen","name":"therascreen KRAS RGQ PCR Kit","cutoff":"Wild-type required for cetuximab or panitumumab (colorectal); G12C detected for sotorasib and adagrasib (NSCLC)"},{"id":"braf-therascreen","name":"therascreen BRAF V600E RGQ PCR Kit","cutoff":"V600E detected (colorectal cancer, encorafenib plus cetuximab)"},{"id":"foundationone-cdx-panel","name":"FoundationOne CDx","cutoff":"Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase"},{"id":"foundationone-liquid-cdx","name":"FoundationOne Liquid CDx","cutoff":"Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue"},{"id":"guardant360-cdx","name":"Guardant360 CDx","cutoff":"Per companion claim: EGFR (osimertinib), EGFR exon 20 insertions (amivantamab), KRAS G12C (sotorasib), ESR1 mutations (elacestrant), ERBB2 mutations (zongertinib); negative plasma reflexes to tissue"},{"id":"oncomine-dx","name":"Oncomine Dx Target Test","cutoff":"Per companion claim: BRAF V600E (dabrafenib plus trametinib), ROS1 fusions (crizotinib), EGFR (gefitinib), RET fusions (pralsetinib), MET exon 14 (tepotinib), EGFR exon 20 insertions"},{"id":"egfr-pharmdx","name":"EGFR pharmDx","cutoff":"Any EGFR membrane staining (historic requirement for cetuximab and panitumumab in colorectal cancer)"}],"resistance":[{"class":"egfr-tki","mechanism":"On-target EGFR C797S","category":"on-target"},{"class":"egfr-tki","mechanism":"MET amplification / bypass","category":"bypass"},{"class":"egfr-tki","mechanism":"Histologic transformation","category":"lineage"},{"class":"kras-g12c","mechanism":"Adaptive RTK feedback (EGFR, others)","category":"bypass"}],"licence":"CC BY-NC 4.0, attribution to OnCo (https://onco.cc); commercial use needs a licence"}