Sym004 induces rapid internalization and degradation of the EGFR that leads to down-modulation of EGFR and subsequent inhibition of cancer cell growth. The inhibition of EGFR with two antibodies contained in Sym004 results in a mechanism of action that is distinct from the more limited actions of single anti-EGFR antibodies.
Biomarker-defined patient selection in mCRC
In the current era of precision medicine, almost all mCRC patients are tested for the genetic biomarkers RAS and BRAF to guide targeted therapy. It is well-known, that mutations in these proteins involved in directing cell growth, cell division or tissue signaling are predictive of a very poor response to anti-EGFR mAb therapy. Approximately 10-20 percent of patients who receive initial treatment with an anti-EGFR mAb therapy respond to such treatment.
However, patients who initially respond ultimately progress while on therapy. Mutations in RAS and BRAF are associated with primary or acquired anti-EGFR resistance in mCRC. In addition, mutations in the extra-cellular domain of EGFR (EGFR-ECD) are believed to be associated with acquired resistance.
Efficacy of Sym004 in Patients With Metastatic Colorectal Cancer With Acquired Resistance to Anti-EGFR Therapy and Molecularly Selected by Circulating Tumor DNA Analyses
Colorectal cancer market facts
In 2021, an estimated 505,000 patients will be diagnosed with CRC in the United States, the five major EU countries (France, Germany, Italy, Spain, and the United Kingdom) and Japan. A further 550,000 patients will be diagnosed in China.
The 2020 market for mCRC-targeted therapies was estimated at USD 5.5 billion in the United States, the five major EU countries (France, Germany, Italy, Spain, and the United Kingdom) and Japan. The market is dominated by anti-VEGF compounds, primarily Avastin® (bevacizumab), with sales estimated at USD 2.6 billion, and anti-EGFR mAbs, including Erbitux® (cetuximab) and Vectibix® (panitumumab), with sales estimated at USD 1.5 billion
Currently available therapies for patients who have undergone 2-3 previous medicine treatment regimes, and thus considered 3rd or 4th line mCRC patients, generally provide only marginal survival benefit or stabilization..