To characterize United States (U.S.) patient enrollment percentages in oncology multi-regional clinical trials (MRCT) supporting initial biologics license applications (BLAs) and new drug applications (NDAs) approvals between 2020 and 2025.
Method
U.S. patient enrollment data for initial BLAs/NDAs approved from 2020–2025 were extracted from FDA review documents (Drugs@FDA and FDA Drug Trial Snapshots). Products lacking U.S. patient enrollment information were excluded. Generative AI tool was utilized to complement data collection and review.
Results
53 oncology product approvals were identified in total: 7 in breast cancer, 4 in prostate cancer, 3 in gastrointestinal (GI) cancer, 2 in bladder cancer, 15 in lung cancer, 17 in hematologic cancer, 3 in gynecologic cancer, and 2 in renal cell carcinoma (RCC). Of these, 17 products were approved via single arm trials. For breast, prostate, GI and lung cancer indications: Programs with large global footprint (greater than 20 countries) trended with a lower U.S. enrollment percentage compared to studies with limited number of countries/regions. Hematologic malignancies, bladder cancer, gynecologic cancers, and RCC: Programs generally achieved 20% or greater U.S. enrollment, except for rare indications such as leukemia. While most applications lacked explicit FDA commentary on U.S. enrollment in multidisciplinary reviews, a total of 11 products included commentary emphasizing that global trials must include sufficiently robust and representative U.S. enrollment, both in numbers and demographics, for data to be considered directly applicable to U.S. patients.
Conclusion
Overall, there’s variability seen in U.S. patient enrollment across tumor types to support initial oncology BLA/NDA approvals. The evolving regulatory landscape in the U.S. highlights the need to examine the impact of large global trial footprints on U.S. enrollment. The FDA’s September 2024 draft guidance on multiregional oncology development programs underscores the importance of proportional and representative patient enrollment in oncology clinical trials. Early alignment with the FDA on U.S. enrollment strategy is important, recognizing that enrollment expectations may vary by program. Consistent with the draft guidance, ensuring sufficient U.S. patient enrollment remains critical to generating evidence that is applicable to the U.S. population and aligned with U.S. standards of care. As many of the products studied were approved prior to the issuance of this guidance, future studies will examine enrollment trends in drugs approved subsequently.
