{"entity":{"id":"destiny-crc01","kind":"trial","name":"DESTINY-CRC01","aka":[],"tldr":"The first trial of the HER2 antibody-drug conjugate in bowel cancer. Almost half the strongly HER2-positive tumours shrank, including some that had already failed other HER2 drugs.","summary":"DESTINY-CRC01 enrolled 78 treated patients into three cohorts by HER2 expression: cohort A (IHC 3+ or IHC 2+ and ISH-positive, 53 patients), cohort B (IHC 2+, ISH-negative, seven) and cohort C (IHC 1+, 18). In cohort A the confirmed objective response rate was 45.3 percent (95% CI 31.6 to 59.6) after a median 27.1 weeks. Grade 3 or worse events in at least a tenth of participants were decreased neutrophil count (22 percent) and anaemia (14 percent); five patients (6 percent) had adjudicated interstitial lung disease or pneumonitis, two of them fatal, the only treatment-related deaths. DESTINY-CRC02 then tested the lower 5.4 mg/kg dose (response 37.8 percent) which is the dose in the April 2024 tumour-agnostic HER2 IHC 3+ accelerated approval.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT03384940","url":"https://clinicaltrials.gov/study/NCT03384940"},{"label":"DESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer (Lancet Oncology 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00086-3"}],"tags":[],"related":[],"cancers":["colorectal","her2-amplified-colorectal"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["tumour-agnostic"],"trials":["destiny-crc02","mountaineer"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03384940","phase":"2","setting":"HER2-expressing metastatic colorectal cancer, RAS and BRAF V600E wild-type, after two or more previous regimens: trastuzumab deruxtecan 6.4 mg/kg, in three cohorts by HER2 level","sponsor":"Daiichi Sankyo","result":"Confirmed objective response 45.3 percent in HER2-positive disease; interstitial lung disease in 6 percent, two deaths.","yearReported":2021,"enrolled":86,"enrolledBasis":"treated","enrolledNote":"The registry lists 86 enrolled; 78 patients received at least one dose and are the reported population.","outcomes":[{"endpoint":"Confirmed objective response rate (cohort A, HER2-positive)","primary":true,"unit":"percent","arms":[{"name":"Trastuzumab deruxtecan 6.4 mg/kg","n":53,"value":45.3}],"ci":[31.6,59.6],"source":"https://doi.org/10.1016/S1470-2045(21)00086-3"}],"replication":"DESTINY-CRC02 confirmed activity at 5.4 mg/kg (ORR 37.8 percent) with a better safety profile."},"route":"/trials/destiny-crc01/","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":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"term":[{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"destiny-crc02","kind":"trial","name":"DESTINY-CRC02","route":"/trials/destiny-crc02/"},{"id":"mountaineer","kind":"trial","name":"MOUNTAINEER","route":"/trials/mountaineer/"},{"id":"triumph","kind":"trial","name":"TRIUMPH","route":"/trials/triumph/"}]}}