Zai Lab Limited announced that the China National Medical Products Administration has accepted the New Drug Application for margetuximab, an investigational, Fc-engineered monoclonal antibody that targets HER2. The margetuximab NDA is for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease, in combination with chemotherapy. In December 2020, MacroGenics Inc. announced that the U.S. Food and Drug Administration (FDA) approved margetuximab (brand name MARGENZA®) in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

The approval was based on efficacy and safety results from the pivotal Phase 3 SOPHIA trial. In October 2021, Zai Lab announced that the bridging study of margetuximab plus chemotherapy as compared with trastuzumab plus chemotherapy in advanced, previously treated HER2-positive breast cancer patients met its primary endpoint, median PFS evaluated by blinded independent central review (BICR). The safety profile was consistent with that seen in the SOPHIA study.

Zai Lab is planning to present the detailed study results at an upcoming medical conference. MARGENZA (margetuximab-cmkb) is an Fc-engineered monoclonal antibody that targets the HER2 oncoprotein. HER2 is expressed by tumor cells in breast, gastroesophageal and other solid tumors.

Similar to trastuzumab, margetuximab-cmkb inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC). However, through MacroGenics' Fc Optimization technology, margetuximab-cmkb has been engineered to enhance the engagement of the immune system. In vitro, the modified Fc region of margetuximab-cmkb increased binding to the activating Fc receptor FCGR3A (CD16A) and decreased binding to the inhibitory Fc receptor FCGR2B (CD32B).

These changes led to greater in vitro ADCC and NK cell activation. The clinical significance of in vitro data is unknown.