The FDA on Monday released new draft guidance on conducting multi-regional oncology trials, saying its “paramount consideration” is whether the results apply to the intended use population and standard cancer care practices in the US.
The draft’s release coincides with the European Society for Medical Oncology’s conference in Barcelona this week, and it comes more than two years after the FDA shut the door on companies only relying on data from China-based trials for new cancer drug approvals.
Back in 2022, the regulator issued a complete response letter to Eli Lilly and Innovent’s sintilimab regarding its China-only data. The agency similarly rejected Hutchmed’s surufatinib, a kinase inhibitor that blocks VEGFR and FGFR, as a treatment of pancreatic and extrapancreatic neuroendocrine tumors, citing similar concerns.
While the FDA’s new nine-page draft doesn’t specifically mention China, it notes that there has been a “decreasing proportion of US participants” in cancer drug trials. If a sponsor is planning a multi-regional trial to support a new drug approval, the FDA recommends “that such a trial be conducted across major geographical regions (e.g., across several continents) rather than predominantly in a single country or in a single geographical region (e.g., Asia).”
The guidance said sponsors should be aware that if a trial’s participant demographics differ significantly from the US population, “foreign data may not be appropriate to support an FDA regulatory decision.”
However, the agency also said there are some circumstances in which it may be acceptable for a sponsor to conduct a multi-regional trial. That includes enrolling “a substantial proportion of participants in a single foreign geographical region if such a trial is conducted as part of an overall program that includes one or more additional pivotal trials in the premarket setting that will enroll a population that is representative of the US population.”
For trials of drugs intended to treat cancers that are common in the US like colorectal or breast cancer, the FDA recommends “equal allocation of study participants across the selected major geographical regions, including North America.” Equal allocation is defined as using equal numbers of subjects from each region.
And for studies in cancers that occur “much less commonly in the US compared to regions outside the US (e.g., squamous cell esophageal cancer), FDA recommends a proportional allocation approach.” Proportional allocation is defined by the draft as the allocation of subjects to regions in proportion to the size of the region and disease prevalence.
The FDA also said companies should take into account patient-related factors like disease risk and genetic background in addition to disease-related and socio-cultural factors, including diet, when deciding if a multi-regional trial is appropriate.
Sponsors should request a meeting with the regulator if and when the treatment landscape changes during a trial to determine the most efficient approach to incorporating those changes into an ongoing trial.