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Rosenberg J , Sridhar SS , Zhang J , Smith D , Ruether D , Flaig TW , Baranda J , Lang J , Plimack ER , Sangha R , Heath EI , Merchan J , Quinn DI , Srinivas S , Milowsky M , Wu C , Gartner EM , Zuo P , Melhem-Bertrandt A , Petrylak DP
EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma
J Clin Oncol. 2020 Apr 1;38(10) :1041-1049
PMID: 32031899    PMCID: PMC7106979    URL: https://www.ncbi.nlm.nih.gov/pubmed/32031899
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PURPOSE: To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers the microtubule-disrupting agent, monomethyl auristatin E, to cells that express Nectin-4. METHODS: EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4-expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on >/= 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death ligand-1 [PD-(L)1] inhibitor, including a cohort of patients with mUC who received prior anti-PD-(L)1 therapy. Patients received escalating doses of EV up to 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. Primary objectives were evaluation of safety/tolerability and pharmacokinetics; antitumor activity was a secondary objective. RESULTS: Enrolled patients with mUC (n = 155) were heavily pretreated, with 96% having prior platinum-based chemotherapy and 29% receiving >/= 3 lines of prior treatment. Maximum tolerated dose of EV was not established; however, the recommended phase II dose was identified as 1.25 mg/kg. Rash, peripheral neuropathy, fatigue, alopecia, and nausea were the most common treatment-related adverse events (TRAEs); the most common TRAEs were grade 1-2 in severity. Among the 112 patients with mUC treated with single-agent EV 1.25 mg/kg, the investigator-assessed confirmed objective response rate (ORR) was 43%, and duration of response was 7.4 months. Median overall survival (OS) was 12.3 months, and the OS rate at 1 year was 51.8%. Similar ORR and estimated median OS were observed in patients >/= 75 years of age with and without prior anti-PD-(L)1 treatment, liver metastases, or upper-tract disease. CONCLUSION: Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging. A pivotal phase II and a confirmatory phase III study are ongoing.
Rosenberg, Jonathan Sridhar, Srikala S Zhang, Jingsong Smith, David Ruether, Dean Flaig, Thomas W Baranda, Joaquina Lang, Joshua Plimack, Elizabeth R Sangha, Randeep Heath, Elisabeth I Merchan, Jamie Quinn, David I Srinivas, Sandy Milowsky, Matthew Wu, Chunzhang Gartner, Elaina M Zuo, Peiying Melhem-Bertrandt, Amal Petrylak, Daniel P eng J Clin Oncol. 2020 Apr 1;38(10):1041-1049. doi: 10.1200/JCO.19.02044. Epub 2020 Feb 7.