# Varlitinib

Source: https://onco.cc/drugs/varlitinib/  
OnCo record `varlitinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: historic
- Last checked: 2026-09-24
- Tags: failure
- 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.

## Sources

- TreeTopp, ESMO Open 2022: https://doi.org/10.1016/j.esmoop.2021.100314
- ClinicalTrials.gov NCT03093870: https://clinicaltrials.gov/study/NCT03093870

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/)
- trials: [TreeTopp](https://onco.cc/trials/treetopp/)

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