{"entity":{"id":"her2-tyrosine-kinase-inhibitors","kind":"technology","name":"HER2 tyrosine kinase inhibitors","aka":[],"tldr":"Small pills that block HER2 from inside the cell, complementing antibody drugs; tucatinib is notable for working against brain metastases.","summary":"Lapatinib (2007), neratinib (2017) and tucatinib (2020) are oral kinase inhibitors of HER2, with lapatinib and neratinib also hitting EGFR. Tucatinib, more selective and so less prone to diarrhoea and rash, improved survival with trastuzumab and capecitabine in the HER2CLIMB trial including patients with brain metastases, and gained a colorectal cancer indication in 2023. Neratinib is used as extended adjuvant therapy after trastuzumab.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tucatinib","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tucatinib"}],"tags":[],"related":[],"cancers":["breast-her2-positive","colorectal"],"sections":["targeted-therapy"],"technologies":[],"targets":["her2"],"drugs":["tucatinib","neratinib","lapatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"ATP-competitive inhibitors bind the intracellular kinase domain of HER2, blocking downstream signalling even when antibodies cannot reach the tumour, such as behind the blood-brain barrier.","strengths":["Oral","Activity against brain metastases","Combine with antibodies and chemotherapy"],"limitations":["Diarrhoea, especially with neratinib and lapatinib","Resistance through HER2 mutations and pathway bypass"],"since":2007},"route":"/technologies/her2-tyrosine-kinase-inhibitors/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"lapatinib","kind":"drug","name":"Lapatinib","route":"/drugs/lapatinib/"},{"id":"neratinib","kind":"drug","name":"Neratinib","route":"/drugs/neratinib/"},{"id":"poziotinib","kind":"drug","name":"Poziotinib","route":"/drugs/poziotinib/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"trial":[{"id":"nct04721977","kind":"trial","name":"A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)","route":"/trials/nct04721977/"},{"id":"nct05672524","kind":"trial","name":"A Study of Tucatinib and Trastuzumab in People With Rectal Cancer","route":"/trials/nct05672524/"},{"id":"nct04579380","kind":"trial","name":"Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations","route":"/trials/nct04579380/"},{"id":"beamion-lung-1","kind":"trial","name":"Beamion LUNG-1","route":"/trials/beamion-lung-1/"},{"id":"nct05190445","kind":"trial","name":"Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma","route":"/trials/nct05190445/"},{"id":"nct05230810","kind":"trial","name":"Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.","route":"/trials/nct05230810/"},{"id":"her2climb","kind":"trial","name":"HER2CLIMB","route":"/trials/her2climb/"},{"id":"her2climb-02","kind":"trial","name":"HER2CLIMB-02","route":"/trials/her2climb-02/"},{"id":"her2climb-05","kind":"trial","name":"HER2CLIMB-05","route":"/trials/her2climb-05/"},{"id":"mountaineer","kind":"trial","name":"MOUNTAINEER","route":"/trials/mountaineer/"},{"id":"mountaineer-03","kind":"trial","name":"MOUNTAINEER-03","route":"/trials/mountaineer-03/"},{"id":"nala","kind":"trial","name":"NALA","route":"/trials/nala/"},{"id":"plasmamatch","kind":"trial","name":"plasmaMATCH","route":"/trials/plasmamatch/"},{"id":"nct05868226","kind":"trial","name":"PRE-ISPY Phase I/II Oncology Platform Program","route":"/trials/nct05868226/"},{"id":"nct04430738","kind":"trial","name":"Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers","route":"/trials/nct04430738/"},{"id":"nct05458674","kind":"trial","name":"Tucatinib+Trastuzumab+Eribulin in HER2+ MBC","route":"/trials/nct05458674/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}]}}