Biomarker Landscape of Antibody Drug Conjugates (ADCs) and Bispecific Antibodies in Clinical Trials for Lung Cancer

Abstract

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  Lung cancer remains the leading cause of cancer-related mortality globally, highlighting the critical need for innovative treatment strategies. Despite advancements in therapy, the 5-year survival rate for lung cancer remains low at 26.7%. Novel therapeutic approaches such as antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs) have shown promise in improving outcomes. ADCs offer targeted cancer cell treatment with minimal cytotoxicity to normal cells, while bsAbs can recruit T cells to tumor sites, enhancing immune response without the need for T cell receptor specificity. However, current drug development often lacks a biomarker-driven approach. The study of clinical trials reveals that while 69.6% focus on bsAbs and 30.4% on ADCs, only 47.8% incorporate biomarker testing, primarily using next-generation sequencing (NGS) and immunohistochemistry (IHC). Common targets include EGFR x c-MET and PD-1 x CTLA-4 for bsAbs, and TROP2 and HER2 for ADCs, with topoisomerase inhibitors and monomethyl auristatin E as frequent payloads. Integrating prospective biomarker strategies in future trials is crucial for advancing personalized lung cancer treatments.