On December 9, 2022 Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using its proprietary Engineered Precision Biologics (EPBs) platform to create antibody drug conjugates (ADCs), reported 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 (SABCS) (Press release, Ambrx, DEC 9, 2022, View Source [SID1234625003]). The data presented by the investigator demonstrated 51.7% overall response rate (ORR) by RECIST v1.1 and 100% disease control rate (DCR) after treatment with ARX788 in HER2 positive mBC patients who are resistant or refractory to T-DM1.

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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 (TKIs). The median age was 59 years. The confirmed objective response rate (ORR) per RECIST v1.1 based was 57.1% (4/7). The disease control rate (DCR) was 100% (7/7) 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 (SAEs) and all adverse events (AEs) were well tolerated with no treatment discontinuations from AEs.

Amplification of the human epidermal growth factor receptor 2 (HER2) gene with consequent HER2 protein overexpression occurs in approximately 20% of breast cancers (BC) and is a major driver of tumor development and progression. The HER2-targeted ADC trastuzumab emtansine (T-DM1) 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.

"This preliminary safety and efficacy data in a heavily pretreated population further reinforces our view of the stability and precision underlying Ambrx’s proprietary drug-linker and site-specific conjugation technology for ADC design," said Daniel O’Connor, Chief Executive Officer of Ambrx. "Our unique approach offers highly differentiated biologic design so that we can work towards providing better outcomes for patients with difficult-to-treat cancers."

Two Phase 3 studies and one registration enabled Phase 2 study with ARX788 (ACE-Breast-02, ACE-Gastric-02, and ACE-Breast-08) conducted by Amrbrx’s partner, NovoCodex Biopharmaceuticals, are ongoing in China with projected readouts in 2023.

Sara Hurvitz, M.D., Professor at David Geffen School of Medicine at UCLA, stated, "We are encouraged by the response rates and safety results, particularly given the significant need for new therapies among patients whose disease continues to progress after receiving multiple lines of therapy. We thank the San Antonio Breast Cancer Symposium for accepting our abstract as a Spotlight Poster Discussion presentation and the opportunity to show early results from the ACE-Breast-03 Phase 2 clinical trial."

Presentation highlights:

Presentation Title: ACE-Breast-03: Efficacy and safety of ARX788 in patients with HER2+ metastatic breast cancer previously treated with T-DM1
Presenting Author: Sara Hurvitz, M.D.
Poster Number: PD18-09
Key Highlights:

ARX788 provided clinical benefit to patients previously treated with T-DM1 who had disease progression
Patients treated with ARX788 had a confirmed ORR of 57.1% (4/7 patients) and unconfirmed ORR of 71.4% (5/7 patients)
The disease control rate was 100% (7/7 patients) for patients treated with ARX788
All adverse events were well tolerated with 85.7% of patients experiencing drug-related AEs (any grade) with 0% of AEs leading to discontinuation and 0% of patients experiencing drug-related SAEs
Treatment with ARX788 remains ongoing in this patient population with the median time of ARX788 therapy of 7.2 months
ARX788 is currently being studied in several registrational trials in breast cancer and gastric/GEJ cancer by Ambrx’s partner, NovoCodex Biopharmaceuticals, in China. Ambrx has recently paused the internal development of ARX788 and is seeking to partner ARX788 outside of China.