# ARX788

Source: https://onco.cc/drugs/arx788/  
OnCo record `arx788` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: phase-3
- Last checked: 2026-09-07
- Modality: ADC
- Mechanism: Site-specific pAF conjugation gives homogeneous DAR ~2; non-cleavable linker limits bystander effect but improves stability.
- Payload: AS269 (MMAF-like tubulin inhibitor), DAR ~1.9
- Linker: Non-natural amino acid, non-cleavable

## Sources

- ClinicalTrials.gov NCT04829604 (ACE-Breast-02): https://clinicaltrials.gov/study/NCT04829604

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Site-specific conjugation & linker chemistry](https://onco.cc/technologies/site-specific-conjugation/)
- targets: [HER2](https://onco.cc/targets/her2/)
- companies: [Ambrx](https://onco.cc/companies/ambrx/), [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- trials: [ACE-Breast-02](https://onco.cc/trials/ace-breast-02/), [ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)](https://onco.cc/trials/nct04829604/)
- ideas: [Sequencing HER2 ADCs by payload after T-DXd](https://onco.cc/ideas/idea-her2-adc-sequencing-payload/)

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