2024 World Conference on Lung Cancer (WCLC) - Posters-P2.10B.08 Opportunities for ADC Development in 2L NSCLC Leveraging Predictive Biomarkers

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The document discusses the potential opportunities for developing antibody-drug conjugates (ADCs) for second-line (2L) treatment of metastatic Non-Small Cell Lung Cancer (mNSCLC), emphasizing the importance of predictive biomarkers in enhancing patient outcomes. Despite advances in 2L treatments, options are limited by substantial toxicity and varied effectiveness. ADCs, combining monoclonal antibodies with cytotoxic agents, represent a promising therapeutic approach but require the identification of biomarkers to predict patient response effectively.<br /><br />Key ADCs under consideration include Dato-DXd and HER3-DXd, which target TROP2 and HER3 proteins, respectively. These would be the first non-HER2-targeting ADCs for mNSCLC 2L. The data indicates that while other ADCs like T-DXd have shown efficacy correlating with HER2 mutations, Dato-DXd effectiveness appears consistent regardless of specific biomarkers. This necessitates further research to identify predictive markers for optimizing patient selection.<br /><br />The results from the trials show promising outcomes with ADCs: for instance, T-DXd demonstrated varying response rates in HER2-overexpressing versus HER2-mutated NSCLC cases. Similarly, in the Phase 1b TROPION-LUNG02 trial, the combination of Dato-DXd and pembrolizumab proved effective irrespective of PD-L1 expression levels. Meanwhile, HER3-DXd demonstrated efficacy in the presence of EGFR mutations without dependency on HER3 wild-type heterodimerization.<br /><br />Overall, ADC treatments such as Dato-DXd and HER3-DXd hold substantial potential for mNSCLC 2L, with ongoing research into biomarkers vital for refining treatment paths and improving results. The study underscores the critical need to further explore and validate biomarkers to enhance therapeutic precision and effectiveness in lung cancer treatments.

Asset Subtitle

Bruno Larvol

Meta Tag

Speaker Bruno Larvol

Topic Metastatic NSCLC – Cytotoxic Therapy

Keywords

antibody-drug conjugates

metastatic Non-Small Cell Lung Cancer

predictive biomarkers

Dato-DXd

HER3-DXd

TROP2

HER3 proteins

HER2 mutations

TROPION-LUNG02 trial

EGFR mutations