U.S. patient enrollment in pivotal clinical trials that supported FDA oncology approvals from 2020 to 2025.

Abstract

e23030 Background: Adequate enrollment of U.S. patients in pivotal clinical trials designed to support applications for FDA approval help support applicability of trial results to the U.S. population. We sought to characterize contemporary patterns of U.S. patient enrollment in pivotal clinical trials supporting FDA oncology approvals. Methods: Pivotal clinical trials that supported FDA approvals of oncology indications and/or new patient populations for drug and biologic products from January 1, 2020, to December 31, 2025, were included in this analysis. Clinical trials of cellular and gene therapies were excluded. U.S. patient enrolment was summarized by trial type, product type, cancer type, and treatment setting. FDA review documents for these approvals were examined for documentation of factors supporting applicability of these pivotal trials’ results to the approved U.S. patient populations. Results: A total of 309 pivotal randomized controlled trials (RCTs) and non-RCT cohorts that supported 281 FDA oncology approvals of drugs and non-cellular biologics were included in this analysis. Characteristics of these pivotal trials are summarized in Table 1. In 18 (6.4%) of these approvals, no U.S. patients were enrolled across their pivotal trials. Documented factors that supported applicability of those trials’ results to their relevant U.S. patient populations included: conduct as multiregional clinical trials; similarity of known intrinsic and extrinsic factors in the trial and U.S. patient populations; and absence of trial conduct and/or data integrity issues. Conclusions: This exploratory analysis demonstrates that most FDA oncology approvals are based on pivotal clinical trials that enrolled U.S. patients, albeit with relatively lower U.S. patient enrollment in RCTs, and in pivotal trials in certain cancers and cancer settings. Pivotal trials for oncology indications that do not enroll U.S. patients may have limited applicability to U.S. patients. U.S. patient enrollment in pivotal trials that supported FDA approvals for oncology indications from 2020 to 2025. N Median US enrollment, % 0% US enrollment, % >0% to <10% US enrollment, % ≥10% to <50% US enrollment, % ≥50% US enrollment, % All Trials 309 16.1 6.2 30.7 40.8 22.3 Trial type RCT 177 8.9 7.9 46.3 34.5 11.3 Non-RCT 132 39.5 3.8 9.8 49.2 37.1 Product type Biologics 149 11.1 9.4 37.6 38.9 14.1 Non-biologics 160 24.0 3.1 24.4 42.5 30.0 Cancer type* Lung 49 7.3 8.2 53.1 28.6 10.2 Breast 22 13.4 0 36.4 50.0 13.7 Non-Hodgkin Lymphomas 22 18.6 0 31.8 45.5 22.7 Multiple Myeloma 17 5.0 11.8 41.2 35.3 11.8 Tumor Agnostic 17 37.9 0 5.9 70.6 23.5 Acute Leukemias 16 16.7 12.5 18.8 37.5 31.3 Urothelial 16 16.9 0 23.5 47.1 29.4 Treatment setting CIS/(neo)adjuvant 23 13.1 4.2 33.3 58.3 4.2 1 st line advanced/metastatic 135 11.3 9.6 37.5 34.6 18.4 2 nd and later-line advanced/metastatic 144 24.8 2.8 24.3 45.1 27.8 *Cancers with ≥15 trials; CIS=carcinoma in-situ; N =number of trials.