{"entity":{"id":"selpercatinib","kind":"drug","name":"Selpercatinib","aka":[],"tldr":"Selpercatinib is a selective RET inhibitor approved for any tumour with a RET fusion, with a further label update in July 2026.","summary":"Selpercatinib is a selective RET kinase inhibitor, designed to avoid the off-target VEGFR effects of older multikinase drugs, taken as 160 mg twice daily. LIBRETTO-001 showed a response rate of about 84% in treatment-naive RET-fusion NSCLC, LIBRETTO-431 beat chemo-immunotherapy first line, and LIBRETTO-531 beat cabozantinib or vandetanib in RET-mutant medullary thyroid cancer. It was approved in 2020 for RET-fusion NSCLC and thyroid cancer and RET-mutant MTC, gained a tumour-agnostic RET-fusion indication in 2022, and a July 2026 FDA action is listed among that month's oncology approvals. Hypertension, raised transaminases and QT prolongation are the main adverse events. Acquired resistance through RET solvent-front mutations and bypass pathways is the current limit. For a newcomer: a pill that works wherever a RET fusion drives the cancer, regardless of organ.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Selpercatinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Selpercatinib"},{"label":"NICE TA911: selpercatinib for untreated RET fusion-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta911"},{"label":"NICE TA1042: selpercatinib for previously treated RET fusion-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta1042"}],"tags":[],"related":["ret-fusion"],"cancers":["thyroid","nsclc","medullary-thyroid-cancer","papillary-thyroid-cancer","ret-fusion-nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["ret"],"drugs":[],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["cancer-drugs-fund"],"trials":["nct03157128","nct04280081","nct03899792","nct04819100","libretto-431"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Retevmo","modality":"Small-molecule kinase inhibitor (RET)","mechanism":"Highly selective RET TKI.","approvals":[{"region":"US","year":2020,"indication":"RET-fusion NSCLC and thyroid; RET-mutant MTC"},{"region":"US","year":2022,"indication":"RET-fusion solid tumours (tumour-agnostic)"},{"region":"US","year":2026,"indication":"Label update (July 2026)"},{"region":"EU","year":2021,"indication":"EU brand Retsevmo"},{"region":"England (NICE)","year":2023,"indication":"Untreated RET fusion-positive advanced non-small-cell lung cancer","note":"TA911, published 26 July 2023, recommends selpercatinib with managed access only, under a managed access agreement."},{"region":"England (NICE)","year":2025,"indication":"Previously treated RET fusion-positive advanced non-small-cell lung cancer not previously treated with a RET inhibitor","note":"TA1042, published 19 February 2025, routine commissioning subject to the commercial arrangement."}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of RET fusion and mutant proteins","Phosphorylation of downstream substrates stops","Highly selective; spares VEGFR, avoiding multikinase toxicity","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"160 mg twice daily (≥50 kg); 120 mg BID (<50 kg); paediatric by BSA","modifications":"Reduce for hepatotoxicity, QTc, hypertension","monitoring":"LFTs every 2 weeks for 3 months; blood pressure; ECG; TSH; growth plates in children","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Oedema"},{"event":"Diarrhoea"},{"event":"Fatigue"},{"event":"Dry mouth"},{"event":"Hypertension"},{"event":"AST/ALT increased"},{"event":"QT prolongation"},{"event":"Hypersensitivity"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.lillycares.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended for RET-fusion NSCLC and thyroid cancers (TA911, TA742, TA760)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2020-05-08","type":"accelerated-approval","region":"US","note":"Accelerated approval, RET-fusion NSCLC and thyroid cancer, RET-mutant MTC (LIBRETTO-001)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy *"},{"date":"2020-05-08","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals#endnote2","indication":"Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) *"},{"date":"2020-05-08","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Adult patients with metastatic RET fusion-positive Non-Small Cell Lung Cancer (NSCLC)"},{"date":"2022-09-21","type":"accelerated-approval","region":"US","note":"RET-fusion solid tumours (tumour-agnostic, accelerated); full approval in NSCLC","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options *"},{"date":"2022-09-21","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2020 converted to traditional approval 2.4 years after it was granted.","indication":"Adult patients with metastatic RET fusion-positive Non-Small Cell Lung Cancer (NSCLC)"},{"date":"2024-04-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Formulation: Adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy"},{"date":"2024-04-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Formulation: Adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)"},{"date":"2024-04-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Formulation: Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options"},{"date":"2024-05-29","type":"approval","region":"US","note":"Paediatric ≥2 years","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-06-12","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2020 converted to traditional approval 4.1 years after it was granted.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals#endnote2","indication":"Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) *"},{"date":"2024-06-12","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 0.2 years after it was granted.","indication":"Formulation: Adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)"},{"date":"2024-09-27","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2020 converted to traditional approval 4.4 years after it was granted.","indication":"Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy *"},{"date":"2024-09-27","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 0.5 years after it was granted.","indication":"Formulation: Adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy"},{"date":"2026-07-14","type":"conversion","region":"US","note":"Traditional approval, locally advanced or metastatic RET fusion-positive solid tumours","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive","indication":"Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options *"},{"date":"2026-07-14","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 2.3 years after it was granted.","indication":"Formulation: Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options"}]},"route":"/drugs/selpercatinib/","neighbours":{"biomarker":[{"id":"ret-fusion","kind":"biomarker","name":"RET fusion and RET mutation","route":"/biomarkers/ret-fusion/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"medullary-thyroid-cancer","kind":"cancer","name":"Medullary thyroid cancer","route":"/cancers/medullary-thyroid-cancer/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men2-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)","route":"/cancers/men2-syndrome/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"papillary-thyroid-cancer","kind":"cancer","name":"Papillary thyroid cancer","route":"/cancers/papillary-thyroid-cancer/"},{"id":"ret-fusion-nsclc","kind":"cancer","name":"RET fusion-positive non-small-cell lung cancer","route":"/cancers/ret-fusion-nsclc/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"},{"id":"thyroid-cancer-markers","kind":"technology","name":"Thyroglobulin, calcitonin and CEA in thyroid cancer follow-up","route":"/technologies/thyroid-cancer-markers/"}],"target":[{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"term":[{"id":"cancer-drugs-fund","kind":"term","name":"Cancer Drugs Fund (England)","route":"/terms/cancer-drugs-fund/"},{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"nct03899792","kind":"trial","name":"A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors","route":"/trials/nct03899792/"},{"id":"nct03157128","kind":"trial","name":"A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRET","route":"/trials/nct03157128/"},{"id":"nct04280081","kind":"trial","name":"A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer a","route":"/trials/nct04280081/"},{"id":"nct04819100","kind":"trial","name":"A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)","route":"/trials/nct04819100/"},{"id":"libretto-431","kind":"trial","name":"LIBRETTO-431","route":"/trials/libretto-431/"},{"id":"libretto-531","kind":"trial","name":"LIBRETTO-531","route":"/trials/libretto-531/"},{"id":"pediatric-match","kind":"trial","name":"NCI-COG Pediatric MATCH (APEC1621)","route":"/trials/pediatric-match/"}],"drug":[{"id":"pralsetinib","kind":"drug","name":"Pralsetinib","route":"/drugs/pralsetinib/"}],"pairing":[{"id":"targeted-before-io-nsclc","kind":"pairing","name":"Sequence: targeted therapy before immunotherapy in driver-positive NSCLC","route":"/pairings/targeted-before-io-nsclc/"}],"person":[{"id":"alexander-drilon","kind":"person","name":"Alexander Drilon","route":"/people/alexander-drilon/"},{"id":"goto-koichi","kind":"person","name":"Koichi Goto","route":"/people/goto-koichi/"},{"id":"lori-wirth","kind":"person","name":"Lori J. Wirth","route":"/people/lori-wirth/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"paper":[{"id":"paper-libretto-001-selpercatinib-nsclc-nejm-2020","kind":"paper","name":"LIBRETTO-001: selpercatinib in RET fusion-positive non-small-cell lung cancer","route":"/key-papers/paper-libretto-001-selpercatinib-nsclc-nejm-2020/"},{"id":"paper-libretto-431-nejm-2023","kind":"paper","name":"LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer","route":"/key-papers/paper-libretto-431-nejm-2023/"},{"id":"paper-libretto-531-nejm-2023","kind":"paper","name":"LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib in advanced RET-mutant medullary thyroid cancer","route":"/key-papers/paper-libretto-531-nejm-2023/"}],"pathway":[{"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":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}