Related Experiment Video
Updated: Apr 20, 2026
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Efficacy, safety, and biomarker analysis of datopotamab deruxtecan in advanced non-small cell lung cancer:
David Planchard1, Nathalie Cozic2, Maria Fernanda Mosele3
1Department of Medical Oncology, Gustave Roussy, 94800 Villejuif, France; IHU PRISM National PRecISion Medecine Center in Oncology, Gustave Roussy, 94800 Villejuif, France.
Abstract:
Antibody-drug conjugates (ADCs) are rapidly transforming the treatment landscape of advanced non-small cell lung cancer (NSCLC), yet validated predictive biomarkers to guide their use remain lacking. ICARUS-LUNG01 is a prospective, phase II study designed to integrate clinical outcomes with longitudinal translational analyses. In this multicenter trial, 100 pretreated patients with advanced NSCLC received the TROP2-directed ADC datopotamab deruxtecan (Dato-DXd). The study reported an objective response rate (ORR) of 26.0%, with a median progression-free survival (PFS) of 3.6 months, and a greater benefit observed in non-squamous tumors. Baseline and on-treatment tumor analyses suggested that resistance to Dato-DXd could be associated with a lack of TROP2 cytoplasmic staining and the early activation of DNA repair pathways. Conversely, the activation of immune-related pathways was associated with treatment response. Validation of these findings in phase III studies will be essential to define biomarkers, ultimately enabling more precise identification of patients most likely to benefit from Dato-DXd.
Insights
Datopotamab deruxtecan (Dato-DXd) shows promise for advanced non-small cell lung cancer (NSCLC). Biomarkers like TROP2 expression and immune pathway activation may predict patient response to this antibody-drug conjugate therapy.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment is evolving with antibody-drug conjugates (ADCs).
- Validated predictive biomarkers for ADC efficacy in NSCLC are currently lacking.
- Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed ADC investigated for NSCLC treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of Dato-DXd in pretreated advanced NSCLC patients.
- To identify potential predictive biomarkers for Dato-DXd response.
- To integrate clinical outcomes with longitudinal translational analyses.
Main Methods:
- Prospective, multicenter, phase II clinical trial (ICARUS-LUNG01).
- 100 pretreated advanced NSCLC patients received Dato-DXd.
- Longitudinal tumor analyses for biomarker discovery.
Main Results:
- Objective response rate (ORR) was 26.0% with median progression-free survival (PFS) of 3.6 months.
- Greater benefit observed in non-squamous NSCLC tumors.
- Lack of TROP2 cytoplasmic staining and early DNA repair pathway activation associated with resistance.
- Activation of immune-related pathways correlated with treatment response.
Conclusions:
- Dato-DXd demonstrates activity in pretreated advanced NSCLC.
- Potential predictive biomarkers include TROP2 expression and immune/DNA repair pathway activation.
- Phase III studies are needed to validate these biomarkers for personalized treatment selection.
More Related Videos
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018