Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, et al. Enfortumab vedotin antibody-drug conjugate targeting Nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 2016;76(10):3003–13.

Article  CAS  PubMed  Google Scholar 

Enfortumab vedotin-ejfv [package insert]. Northbrook, IL: 2023.

Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, et al. EV-101: A phase I study of single-agent enfortumab vedotin in patients eith Nectin-4-positive solid tumors, including metastatic urothelial carcinoma. J Clin Oncol. 2020;38(10):1041–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu AB, Olson D, Snead K, Gosink J, Tenn E, Zaval M, et al., editors. Enfortumab vedotin, an anti-Nectin-4 ADC demonstrates bystander cell killing and immunogenic cell death anti-tumor activity mechanisms of action in urothelial cancers. American Association of Cancer Research Virtual Meeting II; 22–24 June 2020; Virtual.

Olson D, Younan P, Liu B, Blahnik-Fagan G, Gosink J, Snead K, et al. 1187 Enfortumab vedotin induces immunogenic cell death, elicits antitumor immune memory, and shows enhanced preclinical activity in combination with immune checkpoint inhibitors. J Immunother Cancer. 2022;10:A1231.

Google Scholar 

Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(12):1125–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

PADCEV (enfortumab vedotin-ejfv) [package insert] Northbrook, IL [updated April 2023]. Available at: https://astellas.us/docs/PADCEV_label.pdf.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

Article  PubMed  Google Scholar 

Miyazaki J, Nishiyama H. Epidemiology of urothelial carcinoma. Int J Urol. 2017;24(10):730–4.

Article  PubMed  Google Scholar 

National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer stat facts: bladder cancer. Available at: https://seer.cancer.gov/statfacts/html/urinb.html.

Takahashi S, Uemura M, Kimura T, Kawasaki Y, Takamoto A, Yamaguchi A, et al. A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Invest New Drugs. 2020;38(4):1056–66.

Article  CAS  PubMed  Google Scholar 

Rosenberg JE, O’Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2019;37(29):2592–600.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu EY, Petrylak DP, O’Donnell PH, Lee JL, van dHMS, Loriot Y, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):872–82.

Article  CAS  PubMed  Google Scholar 

European Medicines Agency. Padcev: assessment report 2022 [updated 24 Feb 2022]. Available at: https://www.ema.europa.eu/en/documents/assessment-report/padcev-epar-public-assessment-report_en.pdf.

Enfortumab vedotin [package insert]. Leiden: 2022.

Han TH, Gopal AK, Ramchandren R, Goy A, Chen R, Matous JV, et al. CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies. J Clin Pharmacol. 2013;53(8):866–77.

Article  PubMed  PubMed Central  Google Scholar 

Choules MP, Zuo P, Otsuka Y, Garg A, Tang M, Bonate P. Physiologically based pharmacokinetic model to predict drug–drug interactions with the antibody–drug conjugate enfortumab vedotin. J Pharmacokinet Pharmacodyn. 2023. https://doi.org/10.1007/s10928-023-09877-5.

Article  PubMed  Google Scholar 

Yamada A, Fukushi R, Kadokura T, Garg A, Tang M, editors. Absence of ethnic differences in pharmacokinetic profile of enfortumab vedotin between Japanese and non-Japanese patients. In: American Society for Clinical Pharmacology and Therapeutics Annual Meeting, 16–18 March 2022 [poster number P-198].

Li C, Menon R, Walles M, Singh R, Upreti VV, Brackman D, et al. Risk-based pharmacokinetic and drug-drug interaction characterization of antibody-drug conjugates in oncology clinical development: an international consortium for innovation and quality in pharmaceutical development perspective. Clin Pharmacol Ther. 2022;112(4):754–69.

Article  CAS  PubMed  Google Scholar 

Kågedal M, Claret L, Marchand M, Chanu P, Bruno R, Garg A, et al., editors. Herceptin in HER2-positive gastric cancer: evaluation of exposure-response with two dose levels. In: The Population Approach Group Europe (PAGE); 6–9 June 2017; Budapest.

Li C, Wang B, Chen SC, Wada R, Lu D, Wang X, et al. Exposure-response analyses of trastuzumab emtansine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. Cancer Chemother Pharmacol. 2017;80(6):1079–90.

Article  CAS  PubMed  Google Scholar 

Turner DC, Kondic AG, Anderson KM, Robinson AG, Garon EB, Riess JW, et al. Pembrolizumab exposure-response assessments challenged by association of cancer cachexia and catabolic clearance. Clin Cancer Res. 2018;24(23):5841–9.

Article  CAS  PubMed  Google Scholar 

Wang Y, Booth B, Rahman A, Kim G, Huang SM, Zineh I. Toward greater insights on pharmacokinetics and exposure-response relationships for therapeutic biologics in oncology drug development. Clin Pharmacol Ther. 2017;101(5):582–4.

Article  CAS  PubMed  Google Scholar 

Li C, Zhang C, Li Z, Samineni D, Lu D, Wang B, et al. Clinical pharmacology of vc-MMAE antibody-drug conjugates in cancer patients: learning from eight first-in-human Phase 1 studies. MAbs. 2020;12(1):1699768.

Article  PubMed  Google Scholar 

Yamada A, Fukushi R, Kadokura T, Garg A, Tang M, editors. Evaluation of QTc interval in Japanese patients with locally advanced or metastatic urothelial carcinoma following enfortumab vedotin administration. In: American Society for Clinical Pharmacology and Therapeutics Annual Meeting, 16–18 March 2022 [poster number P-199].

Cilliers C, Guo H, Liao J, Christodolu N, Thurber GM. Multiscale modeling of antibody-drug conjugates: Connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy. AAPS J. 2016;18(5):1117–30.

Article  CAS  PubMed  Google Scholar 

Shah DK, Haddish-Berhane N, Betts A. Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin. J Pharmacokinet Pharmacodyn. 2012;39(6):643–59.

Article  PubMed  Google Scholar 

Passey C, Voellinger J, Gibiansky L, Gunawan R, Nicacio L, Soumaoro I, et al. Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. CPT Pharmacometrics Syst Pharmacol. 2023;12(9):1262–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suri A, Mould DR, Liu Y, Jang G, Venkatakrishnan K. Population PK and exposure-response relationships for the antibody-drug conjugate brentuximab vedotin in CTCL patients in the phase III ALCANZA Study. Clin Pharmacol Ther. 2018;104(5):989–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suri A, Mould DR, Song G, Collins GP, Endres CJ, Gomez-Navarro J, et al. Population pharmacokinetic modeling and exposure-response assessment for the antibody-drug conjugate brentuximab vedotin in Hodgkin’s lymphoma in the phase III ECHELON-1 study. Clin Pharmacol Ther. 2019;106(6):1268–79.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kraynov E, Kamath AV, Walles M, Tarcsa E, Deslandes A, Iyer RA, et al. Current approaches for absorption, distribution, metabolism, and excretion characterization of antibody-drug conjugates: an industry white paper. Drug Metab Dispos. 2016;44(5):617–23.

Article  CAS  PubMed  Google Scholar