Trends in U.S and global patient enrollment from 2014 to 2022 in lung cancer clinical trials supporting marketing applications: An FDA analysis.

Oladimeji Akinboro Office of Oncologic Diseases, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD info_outline Oladimeji Akinboro, Vaibhav Kumar, Nicole Lauren Drezner, Erin A. Larkins, Richard Pazdur, Paul Kluetz, Harpreet Singh

Authors Oladimeji Akinboro Office of Oncologic Diseases, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD info_outline Oladimeji Akinboro, Vaibhav Kumar, Nicole Lauren Drezner, Erin A. Larkins, Richard Pazdur, Paul Kluetz, Harpreet Singh Organizations Office of Oncologic Diseases, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, Oncology Center of Excellence, U.S. Food and Drug Administration; Office of Oncologic Diseases, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD Abstract Disclosures Research Funding No funding received None. Background: Oncology drug development is an increasingly global endeavor, however it is unclear how enrollment in registrational clinical trials for lung cancer have been impacted. Clinical trial data must be reflective of the intended population in order to be considered applicable to U.S patients and medical practice, and for FDA review. Methods: Registrational clinical trials supporting lung cancer indications submitted to FDA from 2014 to 2022 were included. Patient enrollment per country was extracted for each trial, and countries were grouped into 9 global regions. The proportion of patients enrolled in the U.S and global regions were calculated for each trial. For the purpose of this analysis, MRCTs were defined as trials that enrolled at least 5% of patients from each of ≥ 3 global regions with no region accounting for ≥ 70% of patient enrollment. Trial-level patient enrollment was aggregated into 3 triennia: 2014-2016, 2017-2019, and 2020-2022. Results: A total of 66 pivotal trials supporting 59 applications submitted to FDA were evaluated during the study period. Of these, 91% ( n =60) were for non-small cell lung cancer while 9% ( n =6) were for small cell lung cancer; 59% ( n =39) were randomized controlled trials (RCTs) while 41% ( n =27) were single-arm trials; 53% ( n =35) were for biologics while 47% ( n =31) were for non-biologics; and 86% ( n =30) of the biologics-based regimens were anti-programmed death (ligand)-1 antibody-containing regimens. The proportion of trials with no U.S patient enrollment increased from 4.8% in 2014-2016 to 19.0% in 2020-2022 while those with ≥ 10% U.S patient enrollment declined from 71.4% in 2014-2016 to 52.3% in 2020-2022. There was a decline in the proportion of trials conducted as MRCTs since 2014 from 85.7% in 2014-2016 to 66.7% in 2020-2022. Conclusions: This exploratory analysis suggests that there may be declining U.S patient enrollment in lung cancer pivotal trials, and the proportion of these trials conducted as MRCTs may also be declining. These patterns of decline appear to be driven by the countries selected for patient enrollment in RCTs rather than in single-arm trials. Pivotal trials that do not enroll U.S patients and are not conducted as true MRCTs may have limited applicability to U.S patients. US patient enrollment in pivotal trials supporting applications for lung cancer indications submitted to FDA from 2014 to 2022. TRIENNIUM TRIALS, n US PATIENT ENROLLMENT, % TRIALS CONDUCTED AS MRCTs, % 0% > 0% to < 10% ≥ 10% ALL TRIALS ( N =66) 2014-2016 21 4.8 23.8 71.4 85.7 2017-2019 24 12.5 33.3 54.2 75.0 2020-2022 21 19.0 28.6 52.3 66.7 RCTs ( N =39) 2014-2016 13 7.7 38.5 53.8 92.3 2017-2019 15 13.3 53.3 33.3 80.0 2020-2022 11 36.4 45.5 18.2 81.8 Single-arm Trials ( N =27) 2014-2016 8 0 0 100 75.0 2017-2019 9 11.1 0 88.9 66.7 2020-2022 10 0 10.0 90.0 50.0 MRCTs=multi-regional clinical trials; N/n =number; RCTs=randomized controlled trials.