FDA Grants Fast Track Designation for HER2-Positive Metastatic Breast Cancer

The FDA has granted a Fast Track designation to ARX788 as a single agent for the treatment of patients with advanced or metastatic HER2-positive breast cancer who received at least 1 prior anti-HER2 regimen in the metastatic setting, Ambrx, Inc. announced in a press release.¹

The presence of HER2 is known to cause cancers to grow more aggressively, and this is overexpressed in about 20% of breast cancers. As many tumors progress following approved HER2-directed therapies, HER2-positive metastatic breast cancer represents a population of unmet medical need.

"This is an important milestone for ARX788 that underscores the strong unmet medical need to develop new and effective treatment options for breast cancer patients whose tumors progressed on currently approved HER2-directed regimens," said Joy Yan, MD, PhD, chief medical officer, Ambrx, in a statement. "It's our mission to drive science forward to help bring innovative therapeutic options to cancer patients and we look forward to working closely with the FDA to optimize and expedite the development of ARX788."

ARX788, a homogeneous and highly stable antibody-drug conjugate (ADC), targets the HER2 receptor and consists of 2 cytotoxic payloads site-specifically conjugated to a trastuzumab (Herceptin)-based antibody. The agent was developed for maximum performance in the preclinical setting by optimizing the number, position, and chemical bounds conjugating the cytotoxic AS269 payload to the antibody.

This designation was granted based on phase 1 clinical trials that assessed the safety, tolerability, and pharmacokinetics of ARX788, as well as preliminary efficacy.

A clinical update on ARX788 was announced in December during a presentation for the 2020 San Antonio Breast Cancer Symposium (SABCS) demonstrated an objective response rate (ORR) of 74% with ARX788 in the phase 1 HER2-positive breast cancer trial in China, which included responses in 14 of 19 patients and a disease control rate (DCR) of 100%. The ORR was 67% in the phase 1 HER2-positive pan tumor trial in the United States and Australia with responses in 2 of 3 patients and a DCR of 100%. Both these findings were found with the 1.5 mg/kg dose.²

The median duration of response (DOR) had not been reached in the 1.5 mg/kg cohort, nor was the median progression-free survival. Overall, the agent appeared well tolerated, and the most common adverse events were mild or moderate and manageable.

"We remain on track to open multiple global ARX788 registrational studies next year, with the first study in HER2-positive breast cancer patients who failed prior T-DM1, T-DXd, or tucatinib-containing regimens starting in early 2021. These global registrational studies are designed to obtain BLA and sBLA in HER2 positive breast cancer, HER2 positive gastric cancer, HER2-low breast cancer, and other HER2-expressing or HER2-mutated solid tumors," stated Yan.

_References

_{1. FDA grants ARX788 fast track designation for HER2-positive metastatic breast cancer. News Release. Ambrx, Inc. January 4, 2021. Accessed January 4, 2021. https://prn.to/3hHuIeF}

_{2. Ambrx presents phase 1 trial data update and phase 2/3 clinical trial in progress for lead program ARX788 at the 2020 San Antonio Breast Cancer Symposium. News Release. Ambrx, Inc. December 10, 2020. Accessed January 4, 2021. https://prn.to/38UXdBK}