ArticleMolecular cancer therapeutics2023
AMT-562, a Novel HER3-targeting Antibody-Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 20 citations in OpenAlex.
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Antibody-drug conjugate-related marker heterogeneity between primary tumors and metastatic lymph nodes in advanced urothelial cancers.Journal of translational internal medicine · 2026Article
- Application of organoid models in basic and translational research of lung cancer: a narrative review.Translational lung cancer research · 2026Review
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Development of SDP0505: a first-in-class HER3 × c-Met bispecific ADC, demonstrates potent antitumor activity in EGFR TKI-resistant NSCLC, CRC, and beyond.Antibody therapeutics · 2026Article
- Roles of Her3 in carcinogenesis and advances in Her3-targeted cancer therapy.Discover oncology · 2026Review
- Innovative use of therapeutic antibodies in lung cancer: the current landscape of ADCs and other antibody-based therapies.Frontiers in oncology · 2026Review
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology.Frontiers in bioengineering and biotechnology · 2026Review
- SPARC: A Multipayload ADC Architecture for Programmable Drug Combinations.Bioconjugate chemistry · 2025Article
- Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.JCI insight · 2025Article
- Novel treatment approaches utilizing antibody-drug conjugates in breast cancer.NPJ breast cancer · 2025Review
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- Checkpoint kinase 1 as a promising target in colorectal cancer management.World journal of clinical oncology · 2025Article
- First-line maintenance strategies and later-line options in patients with advanced gastroesophageal adenocarcinoma.Therapeutic advances in medical oncology · 2025Review
- Lung cancer organoid-based drug evaluation models and new drug development application trends.Translational lung cancer 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
- Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- The Evolving Paradigm of Antibody-Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases.Pharmaceutics · 2024Review
- A Cancer-Specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER3 is a unique member of the EGFR family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting antibody-drug conjugate (ADC) with clinical efficacy in non-small cell lung cancer. However, over 60% of patients are nonresponsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected because of its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS, and tyrosine kinase inhibitor showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetic and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402-insensitive tumors.
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Registered trials
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.