Abstract
<jats:p>Background and Purpose: Rare thoracic tumors face persistent exclusion from clinical trials. To address this, we characterized the representation, geographical distribution, mechanisms of action, and clinical outcomes of Phase I trials in thymic epithelial tumors (TETs) and mesothelioma. Materials and Methods: Phase I solid-tumor trials from Jan 1995 to Jan 2026 were identified on ClinicalTrials.gov and processed using Python to extract trial status. A Python pipeline identified TET and mesothelioma trials and divided them into resulted and non-resulted trials. Resulted trials underwent manual review, and publication status was verified through PubMed, Google Scholar, and LARVOL CLIN. Results: Of 6,610 Phase I trials screened, 3.1% (n=203) included rare thoracic tumors. Among these, 11.3% (n=23) reported results, 34.8% (8/23) advanced beyond Phase I, and 21.7% (n=5) were published in high-impact journals (IF > 10). Targeted therapies dominated classifications (65.2%), followed by immunotherapies (34.8%) and antibody-drug conjugates (ADCs; 8.7%). Reported efficacy outcomes showed wide ranges: objective response rate (ORR, 0-44%), progression-free survival (PFS, 1.3-8.3 months), and overall survival (OS, 3.0-19.3 months). Fatigue was the most frequent toxicity, observed in 58% of targeted therapy trials and 100% of immunotherapy and ADC cohorts. No novel agents achieved subsequent disease-specific FDA approval. Geographically, among 96 trial locations, 49.0% were concentrated in Europe and 21.9% in the United States. Conclusions: Current Phase I trials exhibit a striking scarcity of research for mesothelioma and TETs, concentrated predominantly in high-income regions. Bridging this gap requires prioritizing rare thoracic tumors and building clinical infrastructure in underrepresented countries to enhance trial access and diversity. Keywords: Thymic epithelial tumors, Mesothelioma, Phase I clinical trials, ClinicalTrials.gov, Rare thoracic malignancies.</jats:p>