Biopharmaceutical firm MacroGenics has initiated a Phase II/III clinical trial of margetuximab as a first-line therapy for HER2-positive gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.

The first patient in the trial has already been dosed.

Margetuximab is a monoclonal antibody designed to target the HER2 oncoprotein present in solid tumours, including breast and gastroesophageal cancers.

The investigational drug is also engineered to boost the immune system’s killing of cancer cells via antibody-dependent cellular cytotoxicity (ADCC).

Named MAHOGANY, the two-module Phase II/III trial will investigate margetuximab plus a checkpoint inhibitor, with or without chemotherapy, in advanced or metastatic HER2-positive GEJ/GC.

Module A of the trial is a single-arm study, which will evaluate margetuximab in combination with anti-PD-1 monoclonal antibody MGA012 in patients with HER2-positive and PD-L1-positive tumours.

The primary efficacy outcome is objective response rate (ORR).

Module B will compare margetuximab plus a checkpoint inhibitor and chemotherapy with trastuzumab plus chemotherapy in subjects with HER2-positive tumours, regardless of PD-L1 expression.

Patients will receive either MGA012 or MGD013 to target PD-1 and LAG-3 proteins. The primary efficacy outcome of this module is overall survival (OS).

The trial is being conducted in alliance with Zai Lab, the company’s partner in Greater China.

MacroGenics president and CEO Scott Koenig said: “The MAHOGANY study for patients with gastric or gastroesophageal junction cancer is designed to support registration of margetuximab and is a part of our strategy to advance margetuximab in HER2-positive cancers.

“The combination of margetuximab and a checkpoint inhibitor could potentially provide a chemotherapy-free option as a first-line treatment for patients whose tumours are positive for both HER2 and PD-L1 or be used with chemotherapy in a broader HER2-positive population to improve the clinical activity of existing standard of care.”

In addition to gastric and GEJ cancer, the drug is also being studied in the Phase III SOPHIA trial involving a combination with chemotherapy to treat metastatic HER2-positive breast cancer patients who previously received anti-HER2-targeted therapies.