{"entity":{"id":"heracles","kind":"trial","name":"HERACLES","aka":[],"tldr":"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.\n\nIn 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.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT03225937","url":"https://clinicaltrials.gov/study/NCT03225937"}],"tags":["subtype-trials"],"related":[],"cancers":["her2-amplified-colorectal","colorectal"],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":["trastuzumab","lapatinib","pertuzumab","trastuzumab-emtansine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrea-sartore-bianchi","salvatore-siena"],"bottlenecks":[],"keyPapers":["paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016"],"journals":[],"dependsOn":[],"notes":[],"nct":"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)","result":"Trastuzumab plus lapatinib produced objective responses in roughly a third of refractory HER2-amplified colorectal cancers.","started":"2012-08","yearReported":2016,"enrolled":54,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response (independent central review)","primary":true,"unit":"%","arms":[{"name":"Trastuzumab + lapatinib","n":27,"value":30,"note":"95% CI 14 to 50; median follow-up 94 weeks"}],"source":"https://doi.org/10.1016/S1470-2045(16)00150-9"},{"endpoint":"Stable disease","unit":"%","arms":[{"name":"Trastuzumab + lapatinib","n":27,"value":44}],"source":"https://doi.org/10.1016/S1470-2045(16)00150-9"},{"endpoint":"Grade 3 adverse events","unit":"%","arms":[{"name":"Trastuzumab + lapatinib","n":27,"value":22,"note":"No grade 4 or 5 events"}],"source":"https://doi.org/10.1016/S1470-2045(16)00150-9"}]},"route":"/trials/heracles/","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/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"drug":[{"id":"lapatinib","kind":"drug","name":"Lapatinib","route":"/drugs/lapatinib/"},{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"}],"person":[{"id":"andrea-sartore-bianchi","kind":"person","name":"Andrea Sartore-Bianchi","route":"/people/andrea-sartore-bianchi/"},{"id":"salvatore-siena","kind":"person","name":"Salvatore Siena","route":"/people/salvatore-siena/"}],"paper":[{"id":"paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","kind":"paper","name":"A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","route":"/key-papers/paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011/"},{"id":"paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","kind":"paper","name":"Assessment of a HER2 scoring system for colorectal cancer: results from a validation study","route":"/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/"},{"id":"paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","route":"/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/"},{"id":"paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016","kind":"paper","name":"HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials","route":"/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/"}],"trial":[{"id":"triumph","kind":"trial","name":"TRIUMPH","route":"/trials/triumph/"}],"institution":[{"id":"niguarda-cancer-center","kind":"institution","name":"Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda","route":"/institutions/niguarda-cancer-center/"}]}}