ArticleNature communications2024
The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03451162 (A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer), which is not on this map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer
Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- Advancing antibody drug conjugates in gastrointestinal cancers.British journal of cancer · 2026Review
- ABL209 (NEOK002): Designing an EGFR × MUC1 Bispecific TOP1i ADC with Promising Antitumor Activity and Enhanced Therapeutic Window.Molecular cancer therapeutics · 2026Article
- Ultrasound-Activated Nanoinhibitors Blocking the Chemo-Immune Checkpoint to Overcome Chemotherapy-Induced Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Multi-payload antibody-drug conjugates for photothermal dynamic and chemotherapy of HER2-positive breast cancer.Materials today. Bio · 2026Article
- Restoring the CD226 in CD8Cell death & disease · 2026Article
- Immunosuppressive Microenvironment Reprogramming by Synergistic Sonodynamic Therapy of Phthalocyanine-MOF Hybrids for Hepatocellular Carcinoma.Exploration (Beijing, China) · 2026Article
- Bench-to-Bedside Perspectives on Ocular Toxicity of Antibody-Drug Conjugates: Toxicology, Clinical Management and Molecule Optimization.Pharmaceutical research · 2026Review
- Anti-Trop2-Guided Liposomes Restore Methotrexate Sensitivity in Chemoresistant Gestational Trophoblastic Neoplasia.International journal of nanomedicine · 2026Article
- HER2-Low and HER2-Ultralow Metastatic Breast Cancer and Trastuzumab Deruxtecan: Common Clinical Questions and Answers.Cancers · 2025Review
- Exploiting artificial intelligence in precision oncology: an updated comprehensive review.Journal of translational medicine · 2025Review
- Antibody-Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies.Biomedicines · 2025Review
- Strategic and Chemical Advances in Antibody-Drug Conjugates.Pharmaceutics · 2025Review
- Recent Advances in Bioanalytical Methods for Quantification and Pharmacokinetic Analyses of Antibody-Drug Conjugates.The AAPS journal · 2025Review
- Past, present and future of drug conjugates for cancer therapy.Nature cancer · 2025Review
- Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.JCI insight · 2025Article
- Thio-NHS esters are non-innocent protein acylating reagents.Nature communications · 2025Article
- Exploring immune activation patterns in HER2-low and HER2-ultralow breast cancer subtypes.The oncologist · 2025Article
- Novel treatment approaches utilizing antibody-drug conjugates in breast cancer.NPJ breast cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 10 institutions in 3 countries.
Funding
Abstract
Approved antibody-drug conjugates (ADCs) for HER2-positive breast cancer include trastuzumab emtansine and trastuzumab deruxtecan. To develop a differentiated HER2 ADC, we chose an antibody that does not compete with trastuzumab or pertuzumab for binding, conjugated to a reduced potency PBD (pyrrolobenzodiazepine) dimer payload. PBDs are potent cytotoxic agents that alkylate and cross-link DNA. In our study, the PBD dimer is modified to alkylate, but not cross-link DNA. This HER2 ADC, DHES0815A, demonstrates in vivo efficacy in models of HER2-positive and HER2-low cancers and is well-tolerated in cynomolgus monkey safety studies. Mechanisms of action include induction of DNA damage and apoptosis, activity in non-dividing cells, and bystander activity. A dose-escalation study (ClinicalTrials.gov: NCT03451162) in patients with HER2-positive metastatic breast cancer, with the primary objective of evaluating the safety and tolerability of DHES0815A and secondary objectives of characterizing the pharmacokinetics, objective response rate, duration of response, and formation of anti-DHES0815A antibodies, is reported herein. Despite early signs of anti-tumor activity, patients at higher doses develop persistent, non-resolvable dermal, ocular, and pulmonary toxicities, which led to early termination of the phase 1 trial.
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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.