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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
PubMed

Insights

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.

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