How is Margetuximab different than trastuzumab?

Margetuximab improved objective response rate over trastuzumab: 22% vs 16% (P = . 06; October 10, 2018), and 25% vs 14% (P < . 001; September 10, 2019). Incidence of infusion-related reactions, mostly in cycle 1, was higher with margetuximab (35 [13.3%] vs 9 [3.4%]); otherwise, safety was comparable.

Is Margetuximab FDA approved?

On December 16, the U.S. Food and Drug Administration (FDA) approved margetuximab-cmkb (Margenza) in combination with chemotherapy 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.

What is Margetuximab CMKB?

View Patient Information. A Fc-domain optimized IgG monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2) with potential immunomodulating and antineoplastic activities.

Is trastuzumab a monoclonal antibody?

Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today (Barc).

What is INCMGA00012?

INCMGA00012 is an immunotherapy drug that boosts the body’s natural defenses to fight cancer. Palbociclib is already used to treat certain types of breast cancer; its use in this study is considered investigational. It is taken orally (by mouth). INCMGA00012 is given intravenously (by vein).

What does HER2 mean?

HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). This protein promotes the growth of cancer cells.

What is MGD013?

MGD013 is an investigational bispecific DART molecule that engages PD-1 and LAG-3 with a single molecule, resulting in greater T-cell activation than either a monoclonal antibody alone.

What is the role of trastuzumab?

Trastuzumab is a monoclonal antibody that is used in the treatment of breast cancer. Trastuzumab targets the human epidermal growth factor receptor 2 (HER2) receptor on breast cancer cells that express this tyrosine kinase receptor. These cancers are referred to as HER2-positive breast cancer.

Where is HER2 found?

The HER2 receptor is a 1255 amino acid, 185 kD transmembrane glycoprotein located at the long arm of human chromosome 17 (17q12) [6]. HER2 is expressed in many tissues and its major role in these tissues is to facilitate excessive/uncontrolled cell growth and tumorigenesis [7–9].

What are the effects of Margetuximab on the immune system?

The reduced CD32B binding enhances APC and T-cells activities, resulting in increased immune activation, with more HER2 specific lymphocyte proliferation and antibodies production. There are F and V variants of the CD16A receptors, with similar global distribution but different affinity for the IgG Fc fragment.

How is the Fc fragment of Margetuximab modified?

However, the Fc fragment of margetuximab is modified and engineered to stimulate effectors function.

Which is better Trastuzumab or Margetuximab for ADCC?

However, due to its modified Fc region, margetuximab binds with higher affinity to both CD16A variants and exhibits weaker binding to the inhibitory CD32B Fc receptor, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy compared to trastuzumab. 1, 2, 3, 4, 5

How long is the half life of Margetuximab?

Margetuximab has a geometric mean (%CV) terminal half-life of 19.2 (28%) days. 5