# HERACLES

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

## TL;DR

HERACLES showed that the breast cancer drugs trastuzumab and lapatinib, used together, could shrink bowel cancers that carry extra copies of the HER2 gene, turning a laboratory prediction into a treatment for this small group of patients.

## Summary

Work in patient-derived xenografts had shown that HER2-amplified colorectal cancers respond to dual HER2 blockade. HERACLES was an Italian proof-of-concept phase 2 trial that screened KRAS wild-type metastatic colorectal cancers for HER2 amplification and treated those found, after failure of standard therapies including cetuximab or panitumumab, with trastuzumab plus lapatinib (cohort A). A second cohort tested pertuzumab with trastuzumab emtansine.

In cohort A roughly a third of the heavily pretreated patients had an objective response and responses lasted for many months, establishing HER2 amplification as an actionable target in colorectal cancer and setting up the later MyPathway, MOUNTAINEER and DESTINY-CRC trials.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-17
- Tags: subtype-trials
- Registry id: NCT03225937
- Phase: 2
- Setting: HER2-amplified, KRAS wild-type metastatic colorectal cancer refractory to standard therapy: trastuzumab plus lapatinib (cohort A), and pertuzumab plus trastuzumab emtansine (cohort B)
- Sponsor: Fondazione del Piemonte per l'Oncologia (Candiolo)
- Enrolled: 54
- Result: Trastuzumab plus lapatinib produced objective responses in roughly a third of refractory HER2-amplified colorectal cancers.

## Sources

- ClinicalTrials.gov NCT03225937: https://clinicaltrials.gov/study/NCT03225937

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/)
- drugs: [Lapatinib](https://onco.cc/drugs/lapatinib/), [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/)
- people: [Andrea Sartore-Bianchi](https://onco.cc/people/andrea-sartore-bianchi/), [Salvatore Siena](https://onco.cc/people/salvatore-siena/)
- key papers: [HERACLES: trastuzumab and lapatinib in HER2-amplified, KRAS wild-type metastatic colorectal cancer](https://onco.cc/key-papers/paper-heracles-lancet-oncol-2016/)

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