On December 9, 2021 Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to discover and develop Engineered Precision Biologics (EPBs), reported that NovoCodex Pharmaceuticals Ltd. (NovoCodex), Ambrx’s partner in China, presented positive safety and efficacy data from its ongoing ACE-Breast-01 Phase 1 clinical study of ARX788 at the San Antonio Breast Cancer Symposium (SABCS) (Press release, Ambrx, DEC 9, 2021, View Source [SID1234596704]).

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ACE-Breast-01 is a Phase 1 clinical study of ARX788 in HER2-positive metastatic breast cancer patients whose disease is resistant/refractory to HER2 targeted agents including trastuzumab, ADCs (antibody drug conjugates), TKIs (tyrosine kinase inhibitors) and bispecific antibodies. The updated data, presented during a spotlight poster session (PD8-04), demonstrates ARX788’s robust anti-tumor activity.

Study Highlights

ARX788 at 1.5 mg/kg Q3W demonstrated robust treatment effect as illustrated by objective response rate (ORR) in 29 patients in all prior anti-HER2 treatments groups:
Prior Anti-HER2 Therapy

Confirmed ORR

Trastuzumab containing regimens*

19/29 (66%)

HER2 ADC regimens (T-DM1, DX126-262, A166, BAT8001, HS630)**

4/5 (80%)

HER2 TKI regimens (lapatinib, pyrotinib, neratinib, AST-1306, Hemay-022)

15/23 (65%)

Both HER2 ADC and HER2 TKI regimens

3/4 (75%)

Bispecific antibody containing regimens (KN026 and M802)

3/4 (75%)

Table represents subsets of a total of 29 evaluable patients in the 1.5 mg/kg Q3W cohort, treatment groups are not mutually exclusive

* All patients at 1.5 mg/kg Q3W received prior trastuzumab-containing regimens

** One patient who received prior pertuzumab also achieved confirmed partial response (PR)

The disease control rate among evaluable patients in the 1.5 mg/kg cohort was 100% (29/29)
ARX788 demonstrated low systemic toxicity and was generally well tolerated with most adverse events being grade 1 or 2
No dose limiting toxicity or drug-related deaths occurred
"As the ACE-Breast-01 data for ARX788 continues to develop, we are encouraged by the ADC’s anti-tumor activity and safety profile. ARX788’s ability to continually deliver anti-cancer activity in patients with prior anti-HER2 therapies including ADCs, TKIs and bispecifics, truly highlights the potential of our drug candidate," said Feng Tian, Ph.D., Chairman of the Board, President and CEO of Ambrx. "I look forward to working with NovoCodex to realize the full potential of ARX788."

The Phase 1 clinical study being conducted by our partner, NovoCodex, is a dose escalation study designed to evaluate the safety and anti-tumor activity of ARX788 administered every three weeks in heavily pretreated patients with HER2-positive metastatic breast cancer. The 29 evaluable patients in the 1.5 mg/kg Q3W dose cohort who participated in the study were heavily pretreated with, and had failed, a median of seven prior lines of therapy (median of six for the 69 patients in all cohorts) in the advanced disease setting.

Additionally, Ambrx presented a poster on ACE-Breast-03 in a SABCS ongoing trial poster session (OT1-02-02). The poster details ARX788 in its ongoing global ACE-Breast-03 Phase 2 clinical study in patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens. The study is currently enrolling up to 200 patients and will assess the efficacy, safety and pharmacokinetics of ARX788, with confirmed objective response rate as the primary endpoint.

Dr. Tian continued, "Ambrx’s proprietary EuCODE technology enables ARX788 to maximize the delivery efficiency of the therapeutic’s cytotoxic payload AS269 into HER2-expressing tumor cells. I am looking forward to our on-going global ACE-Breast-03 phase 2 study designed for patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, T-DXd, and tucatinib-containing regimens."