NORTH CHICAGO, Ill.—AbbVie released preliminary results from an ongoing Phase 1 study with ABT-414, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody drug conjugate, in combination with temozolomide, which showed four objective responses, including one complete response, in patients with recurrent or unresectable glioblastoma multiforme. Specifically, one patient experienced a complete response (CR) and three patients experienced partial responses (PR) as measured with the Revised Assessment in Neuro-Oncology (RANO) criteria. These results were presented for the first time at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30 June 3 in Chicago.
"Glioblastoma multiforme is the most common and most aggressive type of malignant primary brain tumor, and patients have few treatment options and a five-year survival rate of less than 3 percent," said Gary Gordon, M.D., divisional vice president, oncology clinical development, AbbVie. "We look forward to continuing evaluations of this compound in additional clinical trials."
The Phase 1, open-label, multicenter, international trial was designed to evaluate the toxicities, pharmacokinetics and recommended Phase 2 dose of ABT-414 when administered every other week in combination with temozolomide in patients with recurrent or unresectable glioblastoma. Other important assessments included adverse events, pharmacokinetic parameters, objective response and tumor tissue epidermal growth factor receptor biomarkers.
"The complete response and three partial responses call for further evaluation of this compound in this extremely difficult-to-treat patient population," said Hui Gan, medical oncologist and senior research fellow at the Austin Health and Ludwig Institute for Cancer Research, Heidelberg, Australia.
ABT-414 is an anti-EGFR (epidermal growth factor receptor) monoclonal antibody drug conjugate (ADC). As an ADC, ABT-414 is designed to be stable in the bloodstream and only release the potent cytotoxic agent once inside targeted cancer cells. Developed by AbbVie researchers with components in-licensed from Life Sciences Pharmaceuticals and Seattle Genetics, ABT-414 is currently being investigated for the treatment of glioblastoma multiforme, the most common and most aggressive malignant primary brain tumor. ABT-414 is also in clinical trials for the treatment of patients with squamous cell tumors. ABT-414 is an investigational compound and its efficacy and safety have not been established by the FDA
Common adverse events (>4 patients) included blurred vision (9 patients), nausea (7 patients), fatigue (6 patients), headache (6 patients), foreign body sensation in the eye (5 patients), photophobia (5 patients), pyrexia (5 patients), corneal deposits (4 patients), eye pain (4 patients) and keratitis (4 patients). Grades 3/4 AEs events (>2 patients) included keratitis (2 patients). Three dose limiting toxicities were reported, including grade 3 corneal deposits (n=1) reported at 1.0 mg/kg, with symptoms improving after a dose reduction, and keratitis (n=1) and gamma-glutamyltransferase increase (n=1), both reported at 1.5 mg/kg.
Later stage clinical trials are being planned to continue to investigate ABT-414 in patients with glioblastoma multiforme.
Each year in the U.S. and Europe, two to three out of every 100,000 people are diagnosed with glioblastoma, which has a five-year survival rate of less than 3 percent. Prior to diagnosis, most patients experience a serious symptom of glioblastoma, such as a seizure. Typically patients succumb to the disease approximately 15 months after diagnosis. Treatment for glioblastoma remains challenging and no long-term treatments are currently available. Standard treatment is surgical resection, radiotherapy and concomitant adjunctive chemotherapy. More than 8,700 patients are enrolled in industry-sponsored clinical studies.3
AbbVie's oncology research is focused on the discovery and development of targeted therapies that work against the processes cancers need to survive. By investing in new technologies and approaches, the company focuses on breaking ground in some of the most widespread and difficult-to-treat cancers, including multiple myeloma and chronic lymphocytic leukemia. Its oncology pipeline includes multiple new molecules in clinical trials being studied in more than 15 different cancers and tumor types.
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.