Dr Garassino on the Potential Use of a TROP2 Biomarker to Predict Outcomes With Dato-DXd in NSCLC

Marina Chiara Garassino, MD, professor, medicine, leader, thoracic program, UChicago Medicine, discusses the potential predictive utility of TROP2 normalized membrane ratio (NMR) for clinical outcomes with datopotamab deruxtecan (Dato-DXd) in patients with previously treated non–small cell lung cancer (NSCLC).

Traditional immunohistochemical (IHC) scoring methods for assessing TROP2 expression have not reliably predicted responses to TROP2-directed antibody-drug conjugates (ADCs) in NSCLC. To improve prediction, an analysis was conducted using quantitative continuous scorring (QCS), a computational pathology approach that measured TROP2 expression both on the cell membrane and within the cytoplasm, Garassino begins. This method was applied to tissue samples from the phase 3 TROPION-Lung01 trial (NCT04656652), which evaluated the efficacy and safety of dato-DXd vs docetaxel in patients with previously treated advanced NSCLC. In this study, tumors were classified as TROP2-QCS biomarker positive if 75% or more of their cells exhibited a TROP2 ratio below a set threshold, indicating a higher cytoplasmic presence of TROP2, she explains.

Findings presented during the 2024 IASLC World Conference on Lung Cancer showed that patients with TROP2-QCS positivity experienced improved outcomes with Dato-DXd compared with those receiving docetaxel, Garassino reports. This was particularly evident in patients with nonsquamous NSCLC, where 66% of patients were positive for the TROP2-QCS biomarker vs44% of patients with squamous NSCLC.

In TROP2-QCS biomarker–positive patients, Dato-DXd reduced the risk of disease progression or death by 43% compared with docetaxel, with a median progression-free survival (PFS) of 6.9 months vs 4.1 months (HR, 0.57; 95% CI, 0.41-0.79), she continues. These findings suggest that TROP2-QCS NMR could serve as a predictive tool for identifying patients who would benefit from Dato-DXd, Garassino explains. Moreover, the threshold for TROP2 positivity was optimized for PFS in patients with nonsquamous NSCLC without actionable genomic alterations, an area of high unmet need. The study also found that the rates of overall and grade 3 or higher toxicities were similar across TROP2 expression levels, she notes. These data indicate that TROP2-QCS-NMR could serve as the first TROP2 biomarker and computational pathology biomarker with predictive value for responses with Dato-DXd in NSCLC, Garassino concludes.