ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular glue that stabilizes the LRPPRC-MET-G4 interaction complex to drive MET downregulation.Nature communications · 2026Article
- Association Between Osimertinib Dose Reduction and Treatment Outcomes in First-Line EGFR-Mutated Advanced NSCLC: The Impact of Post-Progression Management.Thoracic cancer · 2026Article
- Application of organoid models in basic and translational research of lung cancer: a narrative review.Translational lung cancer research · 2026Review
- Bispecific antibody-drug conjugates in cancer: therapeutic-window determinants, tumour-immune interactions, and clinical translation.Frontiers in immunology · 2026Review
- Mechanism of Bispecific Antibodies and Clinical Research Advances in Lung Cancer.Current cancer drug targets · 2026Review
- Innovative use of therapeutic antibodies in lung cancer: the current landscape of ADCs and other antibody-based therapies.Frontiers in oncology · 2026Review
- Targeting MET in advanced and metastatic non-small cell lung cancer: a literature review of the current landscape.Translational cancer research · 2025Review
- Advances in Targeted Therapy for Non-Small-Cell Lung Cancer: Current Progress and Future Directions.International journal of molecular sciences · 2025Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- EGFR Targeted Liposomal PROTAC Assisted With Epigenetic Regulation as an Efficient Strategy for Osimertinib-Resistant Lung Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- JCMM Annual Review on Advances in Biotechnology for the Treatment of Haematological Malignancies: A Review of the Latest In-Patient Developments 2024-2025.Journal of cellular and molecular medicine · 2025Review
- The expanding role of the receptor tyrosine kinase MET as a therapeutic target in non-small cell lung cancer.Cell reports. Medicine · 2025Review
- Review
- Emerging Targets in Non-Small Cell Lung Cancer.Lung Cancer (Auckland, N.Z.) · 2025Review
- The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Lung cancer organoid-based drug evaluation models and new drug development application trends.Translational lung cancer research · 2024Review
- Advanced lung adenocarcinoma withWorld journal of clinical cases · 2024Article
- The MET Oncogene: An Update on Targeting Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.Drug delivery and translational research · 2024Review
- Non-small cell lung cancer organoids: Advances and challenges in current applications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody-drug conjugate targeting MET in MET-driven patient-derived models. EXPERIMENTAL
designPatient-derived organoids, patient-derived cells, or ATCC cell lines were used to investigate the in vitro/in vivo activity of REGN5093-M114.
resultsREGN5093-M114 exhibited significant antitumor efficacy compared with MET TKI or unconjugated METxMET biparatopic antibody (REGN5093). Regardless of MET gene copy number, MET-overexpressed TKI-naïve EGFR-mutant NSCLC cells responded to REGN5093-M114 treatment. Cell surface MET expression had the most predictive power in determining the efficacy of REGN5093-M114. REGN5093-M114 potently reduced tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation after progression on prior osimertinib and savolitinib treatment.
conclusionsAltogether, REGN5093-M114 is a promising candidate to overcome the challenges facing functional MET pathway blockade.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.