Characterizing Exploratory Endpoints in Early Oncology Trials: Insights From Trial Registry Audit
Author(s)
Shaurya Deep Bajwa, MBA, M.Sc.1, VATSAL CHHAYA, M.Sc.2, KAPIL KHAMBHOLJA, PhD2.
1Catalyst Clinical Research, Thiruvananthapuram, India, 2Catalyst Clinical Research, Baroda, India.
1Catalyst Clinical Research, Thiruvananthapuram, India, 2Catalyst Clinical Research, Baroda, India.
OBJECTIVES: Exploratory endpoints in early-phase oncology trials can offer insights into early efficacy signals, biomarker dynamics, and patient outcomes—supporting go/no-go decisions and trial optimization. However, their use remains inconsistent and underreported. This study examined the characteristics and reporting trends of exploratory endpoints in U.S.-registered early-phase oncology trials to identify gaps and opportunities for improved integration.
METHODS: ClinicalTrials.gov was searched for Phase I/II oncology trials with explicitly defined exploratory outcome measures, completed between April 1, 2020, and April 30, 2025. Trials were included if the term “exploratory” appeared in the outcomes section. Descriptive analyses were performed by tumor/cancer type, study design, endpoint category, and measurement scale. Limitations include reliance on registry-reported data and potential misclassification due to inconsistent endpoint labeling.
RESULTS: Among 1,729 eligible trials, only 15 (0.9%) explicitly reported exploratory endpoints. These trials primarily focused on breast (3.7%), prostate (3.5%), multiple myeloma (3.0%), melanoma (2.5%), and acute myeloid leukemia (2.4%). Most used single-arm (60%) and non-randomized (53%) designs. Frequently reported exploratory measures included imaging biomarkers (e.g., RECIST, irRECIST), tumor regression grades, and immune modulation markers. Patient-reported outcomes appeared in 3 trials (17%). Time-based measures dominated, with limited use of quantitative or patient-centered formats—percent/rate (9.8%), score/scale (1.2%), or change from baseline (0.06%). Thresholds for meaningful change were rarely defined. Three trials (20%) were terminated early, with reported issues including interpretation challenges and safety concerns.
CONCLUSIONS: Exploratory endpoints remain underutilized and inconsistently defined in early-phase oncology trials, limiting their translational and regulatory value. Improved standardization and contextualization—potentially through real-world data—may enhance their utility in informing early development decisions and advancing precision oncology.
METHODS: ClinicalTrials.gov was searched for Phase I/II oncology trials with explicitly defined exploratory outcome measures, completed between April 1, 2020, and April 30, 2025. Trials were included if the term “exploratory” appeared in the outcomes section. Descriptive analyses were performed by tumor/cancer type, study design, endpoint category, and measurement scale. Limitations include reliance on registry-reported data and potential misclassification due to inconsistent endpoint labeling.
RESULTS: Among 1,729 eligible trials, only 15 (0.9%) explicitly reported exploratory endpoints. These trials primarily focused on breast (3.7%), prostate (3.5%), multiple myeloma (3.0%), melanoma (2.5%), and acute myeloid leukemia (2.4%). Most used single-arm (60%) and non-randomized (53%) designs. Frequently reported exploratory measures included imaging biomarkers (e.g., RECIST, irRECIST), tumor regression grades, and immune modulation markers. Patient-reported outcomes appeared in 3 trials (17%). Time-based measures dominated, with limited use of quantitative or patient-centered formats—percent/rate (9.8%), score/scale (1.2%), or change from baseline (0.06%). Thresholds for meaningful change were rarely defined. Three trials (20%) were terminated early, with reported issues including interpretation challenges and safety concerns.
CONCLUSIONS: Exploratory endpoints remain underutilized and inconsistently defined in early-phase oncology trials, limiting their translational and regulatory value. Improved standardization and contextualization—potentially through real-world data—may enhance their utility in informing early development decisions and advancing precision oncology.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
SA19
Topic
Patient-Centered Research, Study Approaches
Topic Subcategory
Registries
Disease
Oncology