ArticleMolecular cancer therapeutics2024
Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody-Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04662580 (A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer), which is not on this map. Cited by 14 papers.
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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 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer
Who cites it
14 citing papers in PubMed.
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- Design, Synthesis, and In Vitro Evaluation of a PSMA-Targeted Doxorubicin Conjugate.ChemMedChem · 2026Article
- B7-H3 Gene Expression Shapes Prognosis and Therapeutic Opportunities across Patient Groups with Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- ADC Conjugation Strategies: From Technological Evolution to a Practical Selection Framework.Pharmaceutics · 2026Review
- Emerging evidence for sequencing and combining PSMA-based therapies in prostate cancer.Nature reviews. Urology · 2026Review
- Antibody-Drug Conjugates in Oncology: Principles, Clinical Development, and Future Directions.MedComm · 2026Review
- Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer.Biomedicines · 2026Review
- Antibody-drug conjugates in prostate cancer: current landscape and future directions.Therapeutic advances in medical oncology · 2026Review
- Homogeneous antibody-drug conjugates with dual payloads: potential, methods and considerations.mAbs · 2025Review
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- [Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- PSMA-Directed Theranostics in Prostate Cancer.Biomedicines · 2025Review
- Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Review
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard-of-care androgen deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as an mCRPC tumor antigen with overexpression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids into proteins at selected sites, we have developed ARX517, an antibody-drug conjugate composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a noncleavable polyethylene glycol linker and stable oxime conjugation enabled via synthetic amino acid protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice and dose-dependent antitumor activity in both enzalutamide-sensitive and -resistant cell line-derived xenograft and patient-derived xenograft models of prostate cancer. Repeat-dose toxicokinetic studies in nonhuman primates demonstrated that ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a phase I clinical trial (NCT04662580).
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