ArticlemAbs
Clinical pharmacology of vc-MMAE antibody-drug conjugates in cancer patients: learning from eight first-in-human Phase 1 studies.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- Population pharmacokinetics and exposure-response analyses of polatuzumab vedotin in patients with previously untreated DLBCL from the POLARIX study.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Targeting tumor-selective membrane-associated PCNA enables selective antibody-drug conjugate therapy.Oncoimmunology · 2026Article
- Harnessing Quantitative Medicine to Advance Oncology Drug Development.Clinical and translational science · 2026Review
- Population Pharmacokinetics and Exposure-Response Analyses to Support Cofetuzumab Pelidotin (ABBV-647) Dose Optimization in Non-Small Cell Lung Cancer Patients.Clinical pharmacology and therapeutics · 2026Article
- An Open-Access Dialysis Membrane-Integrated Microfluidic Device for Generating Drug Exposure Profiles Through Molecular-Weight-Dependent Transport.Micromachines · 2026Article
- Evaluating the Impact of Enfortumab Vedotin Dose Modifications on Clinical Efficacy Using Tumor Growth Inhibition Modeling in Patients With Advanced Urothelial Cancer.Journal of clinical pharmacology · 2026Article
- NAV-005, a high-affinity MUC16/CA125 antagonist for the treatment of humoral immunosuppressed cancers.BMC cancer · 2026Article
- Clinical Pharmacology and Translational Science Considerations in the Development of Dual-Payload Antibody Drug Conjugates.Clinical and translational science · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Phenotypic discovery and therapeutic evaluation of anScience advances · 2026Article
- Targeting uPARAP with an Antibody-Drug Conjugate Exhibits Efficacy against Mesothelioma and Synergizes with Cisplatin.Cancer research communications · 2026Article
- A review of targeted drug delivery with antibody-drug complexes.The Journal of pharmacology and experimental therapeutics · 2025Review
- Characterization of Synthesized Ramucirumab-vcMMAE as a Potential Therapeutic Approach in Ovarian Cancer.ACS omega · 2025Article
- 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
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- A Case of Enfortumab Vedotin-Associated Diabetic Ketoacidosis With Severe Insulin Resistance in a Nondiabetic Woman.JCEM case reports · 2024Article
- A novel process for transcellular hemoglobin transport from macrophages to cancer cells.Cell communication and signaling : CCS · 2024Article
- The Vedotin Antibody-Drug Conjugate Payload Drives Platform-Based Nonclinical Safety and Pharmacokinetic Profiles.Molecular cancer therapeutics · 2024Article
- First-in-human study of DP303c, a HER2-targeted antibody-drug conjugate in patients with HER2 positive solid tumors.NPJ precision oncology · 2024Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
vc-MMAE antibody-drug conjugates (ADCs) consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile valine-citrulline (vc) linker. The objective of this study was to characterize the pharmacokinetics (PK) and explore exposure-response relationships of eight vc-MMAE ADCs, against different targets and for diverse tumor indications, using data from eight first-in-human Phase 1 studies. PK parameters of the three analytes, namely antibody-conjugated MMAE (acMMAE), total antibody, and unconjugated MMAE, were estimated using non-compartmental approaches and compared across the eight vc-MMAE ADCs. Relationships between analytes were assessed by linear regression. Exposure-response relationships were explored with key efficacy (objective response rate) and safety (Grade 2+ peripheral neuropathy) endpoints. PK profiles of acMMAE, total antibody and unconjugated MMAE following the first dose of 2.4 mg/kg were comparable across the eight ADCs; the exposure differences between molecules were small relative to the inter-subject variability. acMMAE exposure was strongly correlated with total antibody exposure for all the eight ADCs, but such correlation was less evident between acMMAE and unconjugated MMAE exposure. For multiple ADCs evaluated, efficacy and safety endpoints appeared to correlate well with acMMAE exposure, but not with unconjugated MMAE over the doses tested. PK of vc-MMAE ADCs was well characterized and demonstrated remarkable similarity at 2.4 mg/kg across the eight ADCs. Results from analyte correlation and exposure-response relationship analyses suggest that measurement of acMMAE analyte alone might be adequate for vc-MMAE ADCs to support the clinical pharmacology strategy used during late-stage clinical development.
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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.