ArticleMolecular cancer therapeutics2024
The Vedotin Antibody-Drug Conjugate Payload Drives Platform-Based Nonclinical Safety and Pharmacokinetic Profiles.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Regulatory and Quality Considerations of Antibody-drug Conjugates.AAPS PharmSciTech · 2026Review
- Discovery of a Novel Tripeptide Linker that Broadens the Therapeutic Window of Auristatin-Based Antibody-Drug Conjugates by Reducing Bone Marrow Toxicity.Bioconjugate chemistry · 2026Article
- Clinical Pharmacology and Translational Science Considerations in the Development of Dual-Payload Antibody Drug Conjugates.Clinical and translational science · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Article
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Annexin A1-Targeted d-Peptide-Monomethyl Auristatin E Conjugate Enhanced Antitumor Effect of Monomethyl Auristatin E for Chemotherapy of Prostate Cancer.The Prostate · 2025Article
- Mesothelin-directed protein-drug conjugates for mesothelin-low solid tumor therapy.Nature communications · 2025Article
- First-generation and preclinical evaluation of an EphA5-targeted antibody-drug conjugate in solid tumors.The Journal of clinical investigation · 2025Article
- Auristatin S: An Auristatin Payload with Improved Tolerability and Modified Bystander Activity.ACS medicinal chemistry letters · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonclinical safety and pharmacokinetic data for monomethyl auristatin E (MMAE) and 14 vedotin antibody-drug conjugates (ADC) were evaluated to determine patterns of toxicity, consistency of pharmacokinetic results, and species differences between rats and monkeys. Most nonclinical toxicities were antigen-independent, common across ADCs, and included hematologic, lymphoid, and reproductive toxicity related to MMAE pharmacology. Hematologic toxicity was the dose-limiting toxicity (DLT) or predominant toxicity for the majority of vedotin ADCs in both species. Tissue expression of the targeted antigen of an ADC rarely correlated with DLT; only two ADCs had antigen-dependent skin DLTs. For two additional ADCs, antigen-dependent delivery of MMAE in the bone marrow may have exacerbated the antigen-independent hematologic DLT. The highest tolerated doses and pharmacokinetics were similar within a given species, with rats tolerating higher doses than monkeys. Studies longer than 1 month in duration detected the same or fewer toxicities than 1-month studies and had no additional findings that affected the human risk assessment. These data support opportunities to streamline ADC toxicity assessments without compromising human starting dose selection or target organ identification.
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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.