{"entity":{"id":"amivantamab","kind":"drug","name":"Amivantamab","aka":[],"tldr":"A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.","summary":"Amivantamab is a low-fucose bispecific IgG1 antibody that binds EGFR and MET at once, with enhanced ADCC and trogocytosis. It is approved for EGFR exon 20 insertion NSCLC (2021, with chemotherapy 2024, PAPILLON), first-line common EGFR mutations with lazertinib (MARIPOSA, 2024; OS benefit shown 2025), and post-osimertinib with chemotherapy (MARIPOSA-2). In MARIPOSA the combination extended progression-free survival to 23.7 versus 16.6 months against osimertinib (HR 0.70) and improved overall survival (HR 0.75). The cost is rash, nail toxicity and venous thromboembolism needing prophylactic anticoagulation; a subcutaneous formulation (2025) reduces infusion reactions. Whether the extra benefit justifies the extra burden is still debated. For a newcomer: the first regimen to beat the standard EGFR pill, at the price of more side effects.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Amivantamab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Amivantamab"},{"label":"NICE TA850: amivantamab for EGFR exon 20 insertion mutation-positive advanced non-small-cell lung cancer after platinum-based chemotherapy (not recommended)","url":"https://www.nice.org.uk/guidance/ta850"},{"label":"NICE TA1122: amivantamab with lazertinib for untreated EGFR mutation-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta1122"},{"label":"NICE TA1158: amivantamab with carboplatin and pemetrexed for untreated EGFR exon 20 insertion mutation-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta1158"}],"tags":[],"related":["egfr-exon-19-deletion","egfr-exon-20-insertion"],"cancers":["nsclc","egfr-mutant-nsclc","met-altered-nsclc","lung-cancer"],"sections":[],"technologies":["bispecific-antibody"],"targets":["egfr","met"],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["cancer-drugs-fund","egfr-exon20-insertion"],"trials":["mariposa","nct05801029","nct05379595","nct05498428","nct05663866","nct06667076","nct07276399","nct04538664","nct07586202","nct06120140","nct06662786","nct06385080","nct06750094","nct05908734","nct05488314","nct07227025","nct04988295","chrysalis"],"people":[],"bottlenecks":[],"keyPapers":["paper-mariposa-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"brand":"Rybrevant","modality":"Bispecific antibody (EGFR×MET)","mechanism":"Low-fucose bispecific IgG1 blocking EGFR and MET with enhanced ADCC/trogocytosis.","approvals":[{"region":"US","year":2021,"indication":"EGFR exon 20 insertion NSCLC"},{"region":"US","year":2024,"indication":"First-line EGFR-mutant NSCLC with lazertinib"},{"region":"EU","year":2021,"indication":"Exon 20; 1L with lazertinib Jan 2025"},{"region":"England (NICE)","year":2022,"indication":"Locally advanced or metastatic non-small-cell lung cancer with an EGFR exon 20 insertion after platinum-based chemotherapy: not recommended","note":"TA850, published 14 December 2022, does not recommend amivantamab, so the second-line indication is not funded in England."},{"region":"England (NICE)","year":2026,"indication":"Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with lazertinib","note":"TA1122, published 21 January 2026 (MARIPOSA); must be funded in England within 90 days of publication."},{"region":"England (NICE)","year":2026,"indication":"Untreated advanced non-small-cell lung cancer with an activating EGFR exon 20 insertion, with carboplatin and pemetrexed","note":"TA1158, published 28 May 2026, available during a managed access period under a managed access agreement (PAPILLON)."}],"mechanismSteps":["Bispecific antibody binds EGFR and MET on the tumour cell","Receptor signalling is blocked and receptors are downregulated","Low-fucose Fc recruits macrophages and NK cells (trogocytosis, ADCC)","Tumour cells lose growth signals and are cleared by immune effectors","Lazertinib blocks intracellular EGFR kinase in parallel"],"dosing":{"route":"IV infusion (subcutaneous Rybrevant Faspro available)","schedule":"1,050 mg (<80 kg) or 1,400 mg (≥80 kg) weekly for 5 weeks (split first dose over 2 days), then every 2 weeks; with lazertinib 240 mg daily","modifications":"Hold for grade 3 rash or ILD; dermatologic prophylaxis (doxycycline, moisturisers) for 12 weeks; prophylactic anticoagulation for 4 months with lazertinib","monitoring":"Infusion reactions during first dose, skin and nails, VTE symptoms, ILD","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8"},"toxicity":[{"event":"Rash","anyGradePct":86,"grade3PlusPct":26,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Nail toxicity","anyGradePct":71,"grade3PlusPct":11,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Infusion-related reaction","anyGradePct":63,"grade3PlusPct":6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Musculoskeletal pain","anyGradePct":47,"grade3PlusPct":2.1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Oedema","anyGradePct":43,"grade3PlusPct":2.6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Stomatitis","anyGradePct":43,"grade3PlusPct":2.4,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Venous thromboembolism","anyGradePct":36,"grade3PlusPct":11,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"},{"event":"Paraesthesia","anyGradePct":35,"grade3PlusPct":1.7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","note":"MARIPOSA, with lazertinib"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.janssencarepath.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended with lazertinib for untreated EGFR-mutant NSCLC (2025) and exon 20 insertion after platinum","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-05-21","type":"accelerated-approval","region":"US","note":"Accelerated approval, EGFR exon 20 insertion NSCLC after platinum","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum based chemotherapy"},{"date":"2024-03-01","type":"conversion","region":"US","note":"First-line exon 20 insertion with chemotherapy (PAPILLON)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum based chemotherapy"},{"date":"2024-08-19","type":"approval","region":"US","note":"First-line EGFR-mutant NSCLC with lazertinib (MARIPOSA)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-09-19","type":"approval","region":"US","note":"After osimertinib, with chemotherapy (MARIPOSA-2)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-09","type":"approval","region":"US","note":"Subcutaneous formulation (PALOMA-3)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/amivantamab/","neighbours":{"biomarker":[{"id":"egfr-exon-19-deletion","kind":"biomarker","name":"EGFR exon 19 deletion","route":"/biomarkers/egfr-exon-19-deletion/"},{"id":"egfr-exon-20-insertion","kind":"biomarker","name":"EGFR exon 20 insertion","route":"/biomarkers/egfr-exon-20-insertion/"},{"id":"egfr-l858r","kind":"biomarker","name":"EGFR L858R","route":"/biomarkers/egfr-l858r/"},{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"}],"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"met-altered-nsclc","kind":"cancer","name":"MET exon 14 and MET-amplified non-small-cell lung cancer","route":"/cancers/met-altered-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"term":[{"id":"cancer-drugs-fund","kind":"term","name":"Cancer Drugs Fund (England)","route":"/terms/cancer-drugs-fund/"},{"id":"egfr-exon19-l858r","kind":"term","name":"EGFR exon 19 deletion & L858R","route":"/terms/egfr-exon19-l858r/"},{"id":"egfr-exon20-insertion","kind":"term","name":"EGFR exon 20 insertion","route":"/terms/egfr-exon20-insertion/"},{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"}],"trial":[{"id":"nct06385080","kind":"trial","name":"A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer","route":"/trials/nct06385080/"},{"id":"nct05488314","kind":"trial","name":"A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic 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Cancer","route":"/trials/nct06662786/"},{"id":"nct07227025","kind":"trial","name":"A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer","route":"/trials/nct07227025/"},{"id":"nct07276399","kind":"trial","name":"A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer","route":"/trials/nct07276399/"},{"id":"nct06667076","kind":"trial","name":"A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)","route":"/trials/nct06667076/"},{"id":"nct05498428","kind":"trial","name":"A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung 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Reactions","route":"/trials/nct05663866/"}],"paper":[{"id":"paper-mariposa-nejm-2024","kind":"paper","name":"MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-mariposa-nejm-2024/"}],"drug":[{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"lazertinib","kind":"drug","name":"Lazertinib","route":"/drugs/lazertinib/"}],"pairing":[{"id":"amivantamab-plus-lazertinib","kind":"pairing","name":"Amivantamab + lazertinib (first-line EGFR NSCLC)","route":"/pairings/amivantamab-plus-lazertinib/"},{"id":"tki-then-adc-lung","kind":"pairing","name":"EGFR TKI → ADC on progression","route":"/pairings/tki-then-adc-lung/"}],"person":[{"id":"cho-byoung-chul","kind":"person","name":"Byoung Chul Cho","route":"/people/cho-byoung-chul/"},{"id":"lee-dae-ho","kind":"person","name":"Dae Ho Lee","route":"/people/lee-dae-ho/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"idea":[{"id":"idea-bio1-molecular-progression-add-on","kind":"idea","name":"Add a drug when the blood test turns, without stopping the one that works","route":"/ideas/idea-bio1-molecular-progression-add-on/"},{"id":"idea-bio1-upfront-bypass-combination","kind":"idea","name":"Add the second drug on day one when the escape route is predictable","route":"/ideas/idea-bio1-upfront-bypass-combination/"}],"institution":[{"id":"shanghai-chest-hospital","kind":"institution","name":"Shanghai Chest Hospital","route":"/institutions/shanghai-chest-hospital/"}],"pathway":[{"id":"drug-tolerant-persisters","kind":"pathway","name":"Drug-tolerant persister cells","route":"/pathways/drug-tolerant-persisters/"},{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}