ArticleMolecular cancer therapeutics2022
BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- CRB-701: A Second-generation Nectin-4-Targeted Antibody-Drug Conjugate with Optimized Stability and Pharmacokinetics for the Treatment of Solid Tumors.Cancer research communications · 2026Article
- Cathepsin Family Proteases in Prodrug Design: Recent Advances.ChemMedChem · 2026Review
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- Preclinical Theranostic Study ofACS omega · 2026Article
- Yeast surface display-based screening and preliminary characterization of nectin-4-targeting nanobodies for bladder cancer.BMC biotechnology · 2026Article
- The future of urothelial carcinoma: a 2024-2025 update of early-phase trials of novel therapeutic agents.Current opinion in urology · 2026Review
- Peptides as multifunctional linchpins in targeted drug conjugates.RSC medicinal chemistry · 2026Review
- Bioinformatics profiling of NECTIN4 in lung cancer and comparative evaluation of NECTIN4-targeted ⁶⁸Ga-N188 and ¹⁸F-FDG PET/CT.Journal of translational medicine · 2026Article
- Article
- Bismuth Bicycles.Journal of peptide science : an official publication of the European Peptide Society · 2026Review
- Clinical application and optimization strategies for antibody-drug conjugates in solid tumors.The Journal of international medical research · 2026Review
- Review
- Predictors of Response and Mechanisms of Resistance to Antibody Drug Conjugates in Urothelial Carcinoma.Current oncology (Toronto, Ont.) · 2026Review
- Nectin-4 PET for predicting enfortumab vedotin dose-response in urothelial carcinoma.Science advances · 2026Article
- Research hotspots and frontier analysis of the novel immune checkpoint Nectin-4.Human vaccines & immunotherapeutics · 2025Review
- "Precision on Two Wheels"─Structural Refinement ofJournal of medicinal chemistry · 2025Article
- Antibody-drug conjugates in metastatic urothelial cancer: Highway to heaven.World journal of clinical oncology · 2025Review
- Nectin4-targeted molecular imaging in solid tumors: Current status and future perspectives.View (Beijing, China) · 2025Article
- Mechanistic Insights and Future Directions for Enfortumab Vedotin in Urothelial Carcinoma: Highlights from the 10th Annual Leo & Anne Albert Institute for Bladder Cancer Care and Research Symposium.Current oncology (Toronto, Ont.) · 2025Review
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple tumor types overexpress Nectin-4 and the antibody-drug conjugate (ADC), enfortumab vedotin (EV) shows striking efficacy in clinical trials for metastatic urothelial cancer, which expresses high levels of Nectin-4, validating Nectin-4 as a clinical target for toxin delivery in this indication. Despite excellent data in urothelial cancer, little efficacy data are reported for EV in other Nectin-4 expressing tumors and EV therapy can produce significant toxicities in many patients, frequently leading to discontinuation of treatment. Thus, additional approaches to this target with the potential to extend utility and reduce toxicity are warranted. We describe the preclinical development of BT8009, a "Bicycle Toxin Conjugate" (BTC) consisting of a Nectin-4-binding bicyclic peptide, a cleavable linker system and the cell penetrant toxin mono-methylauristatin E (MMAE). BT8009 shows significant antitumor activity in preclinical tumor models, across a variety of cancer indications and is well tolerated in preclinical safety studies. In several models, it shows superior or equivalent antitumor activity to an EV analog. As a small hydrophilic peptide-based drug BT8009 rapidly diffuses from the systemic circulation, through tissues to penetrate the tumor and target tumor cells. It is renally eliminated from the circulation, with a half-life of 1-2 hours in rat and non-human primate. These physical and PK characteristics differentiate BT8009 from ADCs and may provide benefit in terms of tumor penetration and reduced systemic exposure. BT8009 is currently in a Phase 1/2 multicenter clinical trial across the US, Canada, and Europe, enrolling patients with advanced solid tumors associated with Nectin-4 expression.
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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.