The Henry Ford Cancer Institute was the first research site opened in the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) clinical trial this week. GBM Agile is sponsored by The Global Coalition for Adaptive Research (GCAR). Henry Ford will start enrolling patients immediately.
What is GBM AGILE?
The world’s first global adaptive clinical trial platform for glioblastoma (GBM), and will ultimately evaluate multiple therapies simultaneously across trial sites on multiple continents for patients with newly diagnosed and recurrent GBM—the deadliest of brain cancers.
It is designed as a learning system to more efficiently and rapidly identify effective therapies for GBM patients. The model includes multiple drugs (and combinations of drugs) to be screened simultaneously over time. Drugs that show initial evidence of benefit to patients will seamlessly transition to a confirmatory stage designed to support drug approval. Underperforming drugs are dropped. The intent is to lower the cost, time and number of patients required to evaluate potential new, effective therapies for patients with GBM.
The FDA’s Role: Ms. Woodcock a Tireless Advocate for Industry to Modernize
The FDA has been a strong proponent of modernizing clinical trials with the use of master protocols, including platform trials, to support more efficient and less costly drug development. Janet Woodcock has been a huge advocate for modernization—in fact, this author recounts many times over the last decade she has called for change and commercial sponsors in many cases, continue to lag far behind. Ms. Woodcock was quoted in the press release “Developing new therapies for patients with GBM will require more engagement from industry and enhanced learning from clinical trials. Platform trials can accelerate the time from discovery in the laboratory to implementation in the clinic. GBM AGILE will raise the bar for all clinical trials.”
GBM AGILE Growth
By the end of 2019 GBM AGILE will open in over 40 academic medical centers and community-based institutions across the United States, with plans to expand to Europe, China, Canada, and Australia through 2020.
President of GBM AGILE’S Sponsor: GCAR
Gary Gordon, MD, Ph.D., President of GCAR was quoted “We seek to improve survival in patients with glioblastoma (brain cancer)—of which there is no known prevention or early detection methods, few available treatment options, and no cure.
GBM AGILE First Drug to be Tested: Regorafenib
Although the GBM AGILE platform will test many drugs the first to be tested will be Bayer’s Regorafenib. With a commercial name of Stivarga, it is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic stromal and oncogenic receptor tyrosine kinase (RTK). It has shown anti-angiogenic activity due to its dual targeted VEGRF2-TIE2 tyrosine kinase inhibition. Since 2009, it was studied as a potential treatment option in multiple tumor types. By 2015, it has 2 U.S. FDA approvals for advanced cancers.
Regorafenib showed preliminary efficacy compared to standard of care in the randomized multi-institutional investigator-sponsored Phase II trial REGOMA, published in the Lancet Oncology in December 2018.
The GBM AGILE is an adaptive, global innovative learning environment and an international, seamless Phase II/III response-adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. Its goals are to identify effective therapies for glioblastoma and match effective therapies with patient subtypes. Bayesian response-adaptive randomization is used with subtypes of the disease to assign participants to Arms based on their performance. The primary endpoint is overall survival (OS). The study sponsor is the Global Coalition for Adaptive Research (GCAR) and they will 550 patients.
GBM AGILE is designed to efficiently evaluate therapies. The trial will be conducted under a single Master Investigational New Drug Application/Clinical Trial Application and Master Protocol, allowing multiple drugs and drug combinations from different pharmaceutical companies to be evaluated simultaneously. The plan is to add experimental therapies as new information about promising new drugs are identified and remove therapies as they complete their evaluation.
GCAR’s principal investigator is Tim Cloughesy of UCLA Health.
One of Michigan’s largest cancer institutions, it is the first clinical site for GBM AGILE. Tom Mikkelsen, MD, of the Henry Ford Cancer Institute and medical doctor with Precision Medicine and Clinical Trials at Henry Ford Health System noted “GBM is an aggressive brain tumor with few effective therapies. We are excited to open GBM AGILE and test new treatment options for our patients, who so desperately need them.
The institution includes over 1,300 highly skilled doctors, researchers, nurse navigators and other healthcare specialists providing world-class cancer care to thousands of patients each year. With five hospital locations, six additional outpatient cancer centers and dozens of aligned doctor’s offices, the Commission on Cancer designates Ford as an integrated network—they received in 2016 an Outstanding Achievement Award. Henry Ford is also a Blue Cross Distinction Center for Cancer Care.