Phase I Trial Representation and Geographical Distribution in Mesothelioma and Thymic Epithelial Tumors

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 results and non-resulted. 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 FDA 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.

Highlights

• Rare thoracic malignancies comprised 2.85% of resulted Phase I solid tumor trials in ClinicalTrials.gov

• Zero new investigational drugs reached FDA approval in thymic epithelial tumors

• Targeted therapies represented the predominant investigational treatment strategy

• Fatigue was the top side effect for targeted drugs, immunotherapies, and antibody-drug conjugates

• Clinical trial activity was concentrated in North America and Europe

• Expanding clinical trial networks in underrepresented regions is crucial to improving global diversity and access in Phase I oncology trials