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Targeting internalization, resistance, and response: Insights from ICARUS-LUNG01
Haishuang Sun1, Shen Zhao1, Jing Li1
1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
Cancer Cell
|April 18, 2026
Summary
Datopotamab deruxtecan shows clinical activity in previously treated non-small cell lung cancer (NSCLC). This phase 2 study, ICARUS-LUNG01, investigates biomarkers for antibody-drug conjugate efficacy and resistance in lung cancer patients.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Research
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Effective treatment options for previously treated NSCLC patients are limited.
- Antibody-drug conjugates (ADCs) represent a promising therapeutic strategy for various cancers.
Purpose of the Study:
- To assess the clinical activity of datopotamab deruxtecan in patients with previously treated NSCLC.
- To identify biomarkers predictive of response and resistance to datopotamab deruxtecan.
- To contribute to understanding ADC efficacy in the context of NSCLC treatment.
Main Methods:
- Phase 2, single-arm clinical trial (ICARUS-LUNG01).
- Patients with previously treated advanced NSCLC received datopotamab deruxtecan.
- Biomarker analyses were performed to identify predictive factors.
Main Results:
- Datopotamab deruxtecan demonstrated clinical activity in the studied NSCLC population.
- Specific biomarkers associated with treatment response were identified (details pending full publication).
- The study provides insights into potential resistance mechanisms.
Conclusions:
- Datopotamab deruxtecan is a potential treatment option for previously treated NSCLC.
- Biomarker-driven patient selection may optimize ADC efficacy.
- Further research is warranted to confirm findings and explore resistance pathways.
