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First-in-class antibody mixture shows clinical activity against Tx-resistant, advanced CRC

Date:
May 11, 2015
Source:
American Association for Cancer Research
Summary:
Sym004, a mixture of two anti-epidermal growth factor receptor (EGFR) antibodies, was found to be clinically active in patients with advanced colorectal cancer that had become resistant to prior anti-EGFR therapies.
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Patients with advanced colorectal tumors without mutations in the RAS genes derive substantial benefit from anti-EGFR therapies; however, the disease eventually progresses, leaving these patients with few alternative therapeutic options. Over the last decade, some of the mechanisms driving resistance have been identified, but despite intensive research, treatment options available for patients have not improved, Tabernero said.

Sym004 is a 1:1 mixture in the same infusion bag of two antibodies that bind to different regions of the extracellular domain of EGFR, according toTabernero. Like the U.S. Food and Drug Administration (FDA)-approved anti-EGFR antibodies cetuximab and panitumumab, Sym004 antibodies block EGFR. However, the double-targeting of EGFR by Sym004 causes superior EGFR internalization and degradation, which is likely to provide better outcomes than cetuximab or panitumumab, he explained.

Tabernero and colleagues enrolled 62 patients to a phase I study; 20 patients with advanced solid epithelial tumors were enrolled to the dose-escalation phase of the study and received different doses of Sym004, ranging from 0.4 mg/kg to 12 mg/kg, administered weekly. The remaining 42 patients had metastatic colorectal cancer and had previously been treated with anti-EGFR antibodies with brief responses, and were enrolled to the dose-expansion phase of the trial. Patients in the dose-expansion cohort received weekly doses of 9 mg/kg or 12 mg/kg of Sym004.

Of the patients in the dose-expansion cohort, five (13 percent) had a partial response, and overall, 17 (44 percent) had some degree of tumor shrinkage during treatment with Sym004, according to Tabernero. The overall disease-control rate, which includes partial responses and stable disease, was 67 percent.

Tabernero said that the toxicity profile was consistent with the experience from FDA-approved anti-EGFR antibodies (grade 3 skin toxicity and low magnesium levels, among others) and was controlled with supportive care (topical and systemic antibiotics, and steroids), dose delays, and reductions.

In this research article, Tabernero and colleagues also discussed their preclinical experiments which helped them establish that Sym004 could make colorectal cancer cells overcome acquired resistance to cetuximab.


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Materials provided by American Association for Cancer Research. Note: Content may be edited for style and length.


Journal Reference:

  1. Josep Tabernero et al. Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Cancer Discovery, May 2015 DOI: 10.1158/2159-8290.CD-14-1432

Cite This Page:

American Association for Cancer Research. "First-in-class antibody mixture shows clinical activity against Tx-resistant, advanced CRC." ScienceDaily. ScienceDaily, 11 May 2015. <www.sciencedaily.com/releases/2015/05/150511091553.htm>.
American Association for Cancer Research. (2015, May 11). First-in-class antibody mixture shows clinical activity against Tx-resistant, advanced CRC. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/05/150511091553.htm
American Association for Cancer Research. "First-in-class antibody mixture shows clinical activity against Tx-resistant, advanced CRC." ScienceDaily. www.sciencedaily.com/releases/2015/05/150511091553.htm (accessed May 23, 2017).

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