{"entity":{"id":"her2climb","kind":"trial","name":"HER2CLIMB","aka":[],"tldr":"The first trial to prove a drug helps HER2-positive brain metastases, extending survival by four and a half months overall.","summary":"HER2CLIMB, trial NCT02614794 sponsored by Seagen, now Pfizer, and reported in 2019, was the first trial to prove that a drug helps HER2-positive brain metastases, extending survival overall and in patients with brain disease. It randomised 612 women with HER2-positive metastatic breast cancer after trastuzumab, pertuzumab and trastuzumab emtansine, including 48 percent with active brain metastases, to tucatinib or placebo with trastuzumab and capecitabine, met its primary progression-free survival endpoint, improved overall survival and sharply reduced central nervous system progression, leading to approval in April 2020. OnCo links it to HER2 as a target, tucatinib, trastuzumab, the HER2-positive brain metastases term, Nancy U. Lin and the brain as a bottleneck. Whether systemic therapy should now come before local brain treatment is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02614794","url":"https://clinicaltrials.gov/study/NCT02614794"}],"tags":[],"related":[],"cancers":["breast-her2-positive","secondary-brain-tumours","her2-positive-breast-brain-metastases"],"sections":[],"technologies":["her2-tyrosine-kinase-inhibitors","kinase-inhibitors"],"targets":["her2"],"drugs":["tucatinib","trastuzumab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["her2-brain-metastases"],"trials":[],"people":["nancy-lin"],"bottlenecks":[],"keyPapers":["paper-her2climb-nejm-2020"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02614794","phase":"2","setting":"HER2+ metastatic breast cancer after trastuzumab, pertuzumab, and T-DM1, including active brain metastases: tucatinib + trastuzumab + capecitabine vs placebo + trastuzumab + capecitabine","sponsor":"Seagen (Pfizer)","result":"OS 21.9 vs 17.4 months, HR 0.66; CNS-PFS HR 0.32.","started":"2016-01-28","startedType":"actual","yearReported":2019,"enrolled":612,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Tucatinib arm","n":320,"value":7.8},{"name":"Placebo arm","n":160,"value":5.6}],"hr":0.54,"ci":[0.42,0.71],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1914609"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Tucatinib arm","value":21.9},{"name":"Placebo arm","value":17.4}],"hr":0.66,"ci":[0.5,0.88],"p":"0.005","source":"https://doi.org/10.1056/NEJMoa1914609"}],"replication":"Tucatinib's CNS activity replicated in HER2CLIMB-02 (with T-DM1) and its efficacy in HER2CLIMB-05 (first-line maintenance)."},"route":"/trials/her2climb/","neighbours":{"cancer":[{"id":"secondary-brain-tumours","kind":"cancer","name":"Brain metastases (secondary brain tumours)","route":"/cancers/secondary-brain-tumours/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"}],"technology":[{"id":"her2-tyrosine-kinase-inhibitors","kind":"technology","name":"HER2 tyrosine kinase inhibitors","route":"/technologies/her2-tyrosine-kinase-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"term":[{"id":"her2-brain-metastases","kind":"term","name":"HER2-positive brain metastases","route":"/terms/her2-brain-metastases/"}],"person":[{"id":"nancy-lin","kind":"person","name":"Nancy U. Lin","route":"/people/nancy-lin/"}],"paper":[{"id":"paper-her2climb-brain-lin-jco-2020","kind":"paper","name":"HER2CLIMB brain metastases analysis: intracranial efficacy and survival with tucatinib","route":"/key-papers/paper-her2climb-brain-lin-jco-2020/"},{"id":"paper-her2climb-nejm-2020","kind":"paper","name":"HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases","route":"/key-papers/paper-her2climb-nejm-2020/"}],"pairing":[{"id":"tucatinib-triplet-brain-mets","kind":"pairing","name":"Tucatinib + trastuzumab + capecitabine for brain metastases","route":"/pairings/tucatinib-triplet-brain-mets/"}],"idea":[{"id":"idea-bio2-brain-met-prevention-trials","kind":"idea","name":"Prevention trials aimed only at brain metastasis","route":"/ideas/idea-bio2-brain-met-prevention-trials/"},{"id":"idea-bio2-cns-cohort-mandate","kind":"idea","name":"Stop excluding brain metastases from cancer trials","route":"/ideas/idea-bio2-cns-cohort-mandate/"},{"id":"idea-cns-first-adc-strategy","kind":"idea","name":"Systemic-first management of HER2-positive brain metastases","route":"/ideas/idea-cns-first-adc-strategy/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}]}}