{"entity":{"id":"zidesamtinib","kind":"drug","name":"Zidesamtinib","aka":[],"tldr":"A ROS1 inhibitor approved in July 2026 that works after other ROS1 drugs fail and avoids their brain side effects.","summary":"Zidesamtinib is a ROS1-selective tyrosine kinase inhibitor engineered to spare TRK and penetrate the brain, so it avoids the dizziness and weight gain caused by the TRK activity of repotrectinib and entrectinib while covering the G2032R resistance mutation. It is Nuvalent's first approved drug, cleared in July 2026 for ROS1-positive NSCLC on the ARROS-1 trial, and it is taken once daily. Oedema, fatigue, constipation and raised ALT are the main adverse events reported. It is intended both for patients whose disease has progressed on earlier ROS1 inhibitors and as a better-tolerated option, though its first-line position against repotrectinib and the durability of response are still being defined. Nuvalent's ALK inhibitor neladalkib follows the same selective design. For a newcomer: a ROS1 pill built to work after others fail without the brain side effects.","status":"approved","asOf":"2026-09-04","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Zidesamtinib"}],"tags":[],"related":[],"cancers":["nsclc","ros1-positive-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":[],"companies":["nuvalent"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05118789"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Jideytro","modality":"Small-molecule kinase inhibitor (ROS1)","mechanism":"TRK-sparing, brain-penetrant ROS1-selective TKI.","approvals":[{"region":"US","year":2026,"indication":"ROS1+ NSCLC (July 2026)"}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of ROS1 fusions including G2032R","Phosphorylation of downstream substrates stops","TRK-sparing design avoids dizziness and weight gain","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"Once daily (label dose per July 2026 approval)","monitoring":"LFTs, oedema, neuro-cognitive symptoms (minimised by TRK sparing)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Oedema"},{"event":"Fatigue"},{"event":"Constipation"},{"event":"ALT increased"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-06","type":"designation","region":"US","note":"Breakthrough Therapy designation, ROS1+ NSCLC after prior ROS1 TKI","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-07-22","type":"approval","region":"US","note":"ROS1+ NSCLC after at least one prior ROS1 TKI (ARROS-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zidesamtinib-ros1-positive-non-small-cell-lung-cancer"}]},"route":"/drugs/zidesamtinib/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"company":[{"id":"nuvalent","kind":"company","name":"Nuvalent","route":"/companies/nuvalent/"}],"trial":[{"id":"nct05118789","kind":"trial","name":"A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)","route":"/trials/nct05118789/"}],"drug":[{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"}],"target":[{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}]}}