(Press-News.org) 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.
INFORMATION:
Author Comment: In an interview, Tabernero said, "This study represents one of the first examples of promising translation from preclinical findings to drug development and clinical activity against anti-EGFR antibody-resistant colorectal cancer. The significant antitumor activity of Sym004 in patients whose tumors have become resistant to anti-EGFR therapies suggests that some colorectal cancers that progress after treatment with cetuximab or panitumumab [anti-EGFR therapies] remain dependent on EGFR signaling."
Funding & Disclosures: This study was funded by Symphogen A/S and Merck KGaA. Tabernero is a consultant/advisory board member for Amgen, Imclone, Lilly, Merck KGaA, Millennium, Novartis, Roche, Sanofi, Celgene, Chugai, Taiho, and Symphogen A/S.
To interview Josep Tabernero, contact Amanda Wren at awren@vhio.net or +34-695-207-886. For other inquiries, contact Lauren Riley at lauren.riley@aacr.org or 215-446-7155. Visit our newsroom.
Bottom Line: 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.
Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research
Author: Josep Tabernero, MD, PhD, head of the medical oncology department at Vall d'Hebron University Hospital and director of the Vall d'Hebron Institute of Oncology in Barcelona, Spain
Follow us: Cancer Research Catalyst http://blog.aacr.org; Twitter @AACR; and Facebook http://www.facebook.com/aacr.org
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 35,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in 101 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 25 conferences and educational workshops, the largest of which is the AACR Annual Meeting with almost 19,300 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org. END
The world's first international study on homophobia in sport, "Out on the Fields," has found widespread homophobia in UK sport, prompting calls for a zero tolerance approach towards discrimination and better training for coaches, teachers and officials.
The research, on behalf of the Bingham Cup (the world cup of gay rugby) and affiliated sports groups, was conducted by the global sports market research firm Repucom and overseen by a panel of seven academics from six universities, including Brunel University London.
Participants were from the United Kingdom, Ireland, ...
Sea scallops, one of the most valuable commercial fisheries in the United States, are a well managed and monitored fishery, yet little is known about how changing ocean temperatures and ocean chemistry and other environmental factors could impact the fishery. A new study published May 6 in PLOS ONE describes a new computer model to help inform scallop management discussions and decisions in the coming decades.
Researchers from the Woods Hole Oceanographic Institution (WHOI), NOAA Fisheries' Northeast Fisheries Science Center (NEFSC), and Ocean Conservancy developed an ...
BINGHAMTON, NY -According to new research co-authored by Binghamton University's Seth Spain, there is more than meets the eye when it comes to the impact of Saturday morning cartoons.
The research examines how fantasy-based stories, in particular the popular 1980s cartoon series The Transformers, can shape children's perceptions of what behaviors are associated with effective leadership. It also could provide a basis for workplace-training programs.
"We believe that Transformers presents three key lessons about leadership," said Spain, an assistant professor of organizational ...
Philadelphia, PA, May 7, 2015 - Current U.S. health policy requires Medicaid beneficiaries to wait 30 days before tubal sterilization. Ob/gyn experts argue that this violates health care justice as elective tubal sterilization is readily available to women with a private source of payment. Writing in the American Journal of Obstetrics & Gynecology, they urge obstetricians to advocate for change to eliminate health care injustice in women's access to elective tubal sterilization.
One of the most common forms of contraception in the U.S. is tubal sterilization after childbirth, ...
Some of the most popular social media sites are filled with images of extremely thin women that might be harmful to those who view them -- whether they are seeking them or not, according to research from the University of California, Davis. The images were often cropped to remove heads or focus on just a few body parts.
Doctoral candidate Jannath Ghaznavi and associate professor Laramie Taylor in the Department of Communication examined about 300 photographs from Twitter and Pinterest postings that used the terms "thinspiration" and/or "thinspo" to tag images and ideas ...
URBANA, Ill. - Much attention has been given to dedicated, perennial bioenergy crops to meet the revised Renewable Fuel Standard mandating production of 36 billion gallons of biofuel by the year 2022. Even so, concern remains over the impending need to convert as much as 30 million acres of U.S. crop land, which would include food crops, to land for perennial energy crops in order to meet that demand.
Researchers realize that biomass feedstocks will need to come from many different sources, including crop residues, forest residues, and municipal waste, for example, said ...
Livermore - New results from the NASA NuSTAR telescope show that a supernova close to our galaxy experienced a single-sided explosion.
A team of scientists including Lawrence Livermore National Laboratory researchers found that X-ray emissions taken with the Nuclear Spectroscopic Telescope Array (NuSTAR) show that the Supernova 1987A explosion was highly asymmetric. The results appear in the May 8 edition of the journal, Science.
NuSTAR observations, including those of 1987A, provide strong and compelling observational evidence that supernovae are not symmetric.
Supernova ...
El Salvador, Niger, and Pakistan are performing better in improving water and sanitation for their citizens than industrial giants like Russia and Brazil according to the new WaSH Performance Index developed by The Water Institute at the University of North Carolina at Chapel Hill's Gillings School of Global Public Health. The new index to be released Friday, May 8 during a live webcast shows which countries are leaders in improving access to water and sanitation for their citizens. Sub-Saharan Africa countries including Mali, South Africa, and Ethiopia are also among the ...
(MEMPHIS, Tenn. -- May 8, 2015) St. Jude Children's Research Hospital scientists have gained ground toward developing more targeted therapies for the most common childhood brain tumor. The findings appear today in the Journal of Molecular Biology.
The findings involve the DDX3X gene. In 2012, the St. Jude Children's Research Hospital -- Washington University Pediatric Cancer Genome Project highlighted DDX3X as a promising focus for efforts to develop targeted therapies against medulloblastoma. Such treatments target the genetic mistakes that give rise to the brain tumor's ...
PITTSBURGH -- Scientists have been manipulating genes for a while. The University of Pittsburgh's Alexander Deiters just found a way to control the process with higher precision.
By using light.
Deiters and his group are the first to achieve this. The resulting paper was recently published in the Journal of the American Chemical Society.
Since 2013, scientists have used a gene-editing tool called CRISPR/Cas9. The method employs a bacterially derived protein (Cas9) and a synthetic guide RNA to induce a double-strand break at a specific location in the genome. This ...
