The US Food and Drug Administration (FDA) in 2018 proposed new guidelines for the use of so-called “master protocol” clinical trials, such as basket trials that test a candidate targeted therapy against multiple cancer types — a move the agency hopes will hasten the development of new precision-medicine treatment options.1
Public comments are now being reviewed and addressed and the FDA will issue final guidance late in 2019 or early in 2020, an agency spokesperson told Cancer Therapy Advisor.
Modernizing clinical trial design to include “tissue-agnostic” clinical testing based on biomarkers such as specific gene mutations will reduce the costs of the development of targeted therapies, according to then-outgoing FDA Commissioner Scott Gottlieb, MD. That will improve market competition to bring down prices, Dr Gottlieb said.
“It is very encouraging that FDA released draft master protocol guidance,” said Vivek Subbiah, MD, associate professor, department of investigational cancer therapeutics and center clinical medical director, Center for Targeted Therapy, the University of Texas MD Anderson Cancer Center in Houston.
It’s the latest sign that the FDA is becoming more “patient-centered and focused,” Dr Subbiah said. “Wider use of basket trials would definitely hasten drug development,” he said.
But academia, industry, the National Cancer Institute (NCI), and the FDA have to work together more closely to encourage wider use of master-protocol research for it to truly benefit patients, Dr Subbiah said. (FDA staff recently met with the NCI to begin work on facilitating communication between the FDA and clinical researchers early in the planning of master protocol drug development studies, an FDA spokesperson said.) “The recent NCI-MATCH is an early iteration of this, which tests feasibility of basket trials across multiple sites,” he noted.
Master Protocol Trial Designs: Umbrella, Platform, and Basket
There are 3 types of “master protocol” trials: umbrella trials (which study multiple targeted drugs’ efficacy against a particular type of cancer); platform trials that similarly study multiple targeted therapies against a single disease on an ongoing basis, with candidate therapies entering or leaving the platform; and basket trials.2,3
Basket trials study a single targeted therapy in patients with different cancer types or subtypes, based on biomarker status (for example, based on the validated presence of a particular gene variant or mutation).2,3 Basket trial master protocols can be very complex, with multiple patient stratifications to test multiple biomarkers and candidate therapies.3
cancer clinical trials have been centered on the treatment of cancer based on
the anatomic location in the body, like breast cancer or brain cancer or lung
cancer,” Dr Subbiah said. “A basket study is a novel trial design that includes
patients with [a] certain molecular aberration regardless of the location or
tissue of origin of cancer in the body. The genomic revolution in oncology has
fueled these studies.”
Patients with the same genetic aberration, such as BRAF V600 or TRK fusions, can be included in basket trials regardless of where their cancer originated. Hence, the use of the terms “pan-cancer” and “tissue-agnostic” to describe these studies, Dr Subbiah explained.