{"entity":{"id":"varlitinib","kind":"drug","name":"Varlitinib","aka":[],"tldr":"A pill that blocked the HER family of growth receptors, tested with capecitabine as second-line treatment for bile duct and gallbladder cancer. It did not beat capecitabine alone in the TreeTopp trial and development stopped.","summary":"Varlitinib is an oral reversible inhibitor of EGFR, HER2 and HER4 developed by ASLAN Pharmaceuticals for biliary tract cancer on the rationale that EGFR and HER2 are overexpressed in a quarter to a half of these tumours. The global double-blind TreeTopp phase 2 randomised 127 patients with advanced biliary tract cancer after one gemcitabine-containing line to capecitabine with varlitinib 300 mg twice daily or placebo. Objective response was 9.4 versus 4.8 percent (p 0.42), median progression-free survival 2.83 versus 2.79 months (hazard ratio 0.90) and overall survival 7.8 versus 7.5 months (hazard ratio 1.11); grade 3 or worse adverse events occurred in 66 versus 59 percent. A subgroup analysis suggested a progression-free survival signal in women and in gallbladder cancer (2.9 versus 1.6 months, hazard ratio 0.55, 95 percent confidence interval 0.26 to 1.19), which was hypothesis-generating only. The planned phase 3 part was not pursued and varlitinib is not in development for biliary cancer. It stands as one of several HER-directed small molecules that failed in unselected biliary populations, in contrast to HER2-selected antibody therapy.","status":"historic","asOf":"2026-09-24","links":[{"label":"TreeTopp, ESMO Open 2022","url":"https://doi.org/10.1016/j.esmoop.2021.100314"},{"label":"ClinicalTrials.gov NCT03093870","url":"https://clinicaltrials.gov/study/NCT03093870"}],"tags":["failure"],"related":[],"cancers":["gallbladder","cholangiocarcinoma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["egfr","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["treetopp"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"ASLAN001, ARRY-334543","modality":"Small-molecule reversible pan-HER kinase inhibitor (EGFR, HER2, HER4)","mechanism":"ATP-competitive reversible inhibition of EGFR, HER2 and HER4 kinases.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/varlitinib/","neighbours":{"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"trial":[{"id":"treetopp","kind":"trial","name":"TreeTopp","route":"/trials/treetopp/"}]}}