EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma

被引：218

作者：

Rosenberg, Jonathan ^{[1
]}

Sridhar, Srikala S. ^{[2
]}

Zhang, Jingsong ^{[3
]}

Smith, David ^{[4
]}

Ruether, Dean ^{[5
]}

Flaig, Thomas W. ^{[6
]}

Baranda, Joaquina ^{[7
]}

Lang, Joshua ^{[8
]}

Plimack, Elizabeth R. ^{[9
]}

Sangha, Randeep ^{[10
]}

Heath, Elisabeth I. ^{[11
]}

Merchan, Jamie ^{[12
]}

Quinn, David I. ^{[13
]}

Srinivas, Sandy ^{[14
]}

Milowsky, Matthew ^{[15
]}

Wu, Chunzhang ^{[16
]}

Gartner, Elaina M. ^{[17
]}

Zuo, Peiying ^{[16
]}

Melhem-Bertrandt, Amal ^{[16
]}

Petrylak, Daniel P. ^{[18
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[2] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[3] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[4] Univ Michigan, Ann Arbor, MI 48109 USA

[5] Tom Baker Canc Clin, Calgary, AB, Canada

[6] Univ Colorado, Comprehens Canc Ctr, Aurora, CO USA

[7] Univ Kansas, Canc Ctr, Fairway, KS USA

[8] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA

[9] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[10] Cross Canc Inst, Edmonton, AB, Canada

[11] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA

[12] Univ Miami, Miami, FL USA

[13] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90007 USA

[14] Stanford Univ, Stanford, CA 94305 USA

[15] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[16] Astellas Pharma, Northbrook, IL USA

[17] Seattle Genet, Bothell, WA USA

[18] Yale Sch Med, New Haven, CT USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 10期

关键词：

CISPLATIN;

D O I：

10.1200/JCO.19.02044

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSETo 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.METHODSEV-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.RESULTSEnrolled 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.CONCLUSIONSingle-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. (c) 2020 by American Society of Clinical Oncology

引用

页码：1041 / +

页数：11

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