{"entity":{"id":"arx788","kind":"drug","name":"ARX788","aka":[],"tldr":"ARX788 is a HER2 ADC with a precisely placed, non-cleavable payload that beat lapatinib-capecitabine in China and showed activity in brain metastases.","summary":"ARX788 is a HER2 antibody-drug conjugate in which the payload is attached at a precisely engineered non-natural amino acid (pAF), giving a homogeneous drug-to-antibody ratio of about 2; its non-cleavable linker limits the bystander effect but improves stability in circulation. Developed by Ambrx (acquired by Johnson & Johnson in 2024) and NovoCodex, it is aimed at HER2-positive metastatic breast cancer. The ACE-Breast-02 phase 3 trial showed PFS of 11.3 versus 8.2 months (HR 0.64) against lapatinib plus capecitabine, and ACE-Breast-06 showed intracranial activity in active brain metastases. Ocular and interstitial lung toxicities are the main concerns. It holds FDA Fast Track designation and a Chinese marketing application is planned; how it will be positioned against T-DXd is unclear. For a newcomer, it is a HER2 ADC with a precisely placed payload that showed activity in the brain.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04829604 (ACE-Breast-02)","url":"https://clinicaltrials.gov/study/NCT04829604"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc","site-specific-conjugation"],"targets":["her2"],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":["ace-breast-02","nct04829604"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"ADC","payload":"AS269 (MMAF-like tubulin inhibitor), DAR ~1.9","linker":"Non-natural amino acid, non-cleavable","mechanism":"Site-specific pAF conjugation gives homogeneous DAR ~2; non-cleavable linker limits bystander effect but improves stability.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/arx788/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"ambrx","kind":"company","name":"Ambrx","route":"/companies/ambrx/"},{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"trial":[{"id":"ace-breast-02","kind":"trial","name":"ACE-Breast-02","route":"/trials/ace-breast-02/"},{"id":"nct04829604","kind":"trial","name":"ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)","route":"/trials/nct04829604/"}],"idea":[{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/"}]}}