Ambrx Biopharma announces preliminary data from ACE-Breast-03 study

Ambrx Biopharma announced preliminary safety and efficacy data from its Phase 2 ACE-Breast-03 study during a Spotlight Poster Presentation at the 2022 San Antonio Breast Cancer Symposium, or SABCS. The data presented by the investigator demonstrated 51.7% overall response rate, or ORR, by RECIST v1.1 and 100% disease control rate, or DCR, after treatment with ARX788 in HER2 positive mBC patients who are resistant or refractory to T-DM1. ACE-Breast-03 is a Phase 2, multicenter study of ARX788, an anti-HER2 ADC being evaluated for patients whose metastatic disease is resistant or refractory to T-DXd, T-DM1, or tucatinib-containing regimens. The study was conducted in the U.S., Korea, and Australia. As of the data cutoff, seven patients enrolled in the study were previously treated with T-DM1 and received a median of five lines of prior anticancer therapies. Four of seven patients were previously treated with HER2 tyrosine kinase inhibitors, or TKIs. The median age was 59 years. The confirmed objective response rate, or ORR, per RECIST v1.1 based was 57.1%. The disease control rate was 100% for patients treated with ARX788. Patients had a median time on therapy of 7.2 months and treatment remains ongoing. None of the patients experienced drug-related serious adverse events, or SAEs, and all adverse events, or AEs, were well tolerated with no treatment discontinuations from AEs. Amplification of the human epidermal growth factor receptor 2 gene with consequent HER2 protein overexpression occurs in approximately 20% of breast cancers and is a major driver of tumor development and progression. The HER2-targeted ADC trastuzumab emtansine has been approved for the treatment of HER2-positive mBC after prior trastuzumab and taxane therapy. However, disease progression occurs in T-DM1 treated patients and as such, requires additional therapeutic options. The use of second-generation anti-HER2 ADCs using alternative molecules is being investigated to overcome drug resistance. Two Phase 3 studies and one registration enabled Phase 2 study with ARX788 conducted by Amrbrx’s partner, NovoCodex Biopharmaceuticals, are ongoing in China with projected readouts in 2023.