ASCO 2019: EV-201: Results of Enfortumab Vedotin Monotherapy for Locally Advanced or Metastatic Urothelial Cancer Previously Treated with Platinum and Immune Checkpoint Inhibitors

Chicago, IL ( Enfortumab vedotin (EV) is an antibody-drug conjugate comprised of a monoclonal antibody directed against nectin-4 conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE). Nectin-4 is a cancer-associated transmembrane protein expressed in over 80% of bladder cancers.1 EV-101, a phase 1 trial of EV in metastatic urothelial cancer, demonstrated a 45% response rate among anti-PD-1/L1 refractory patients, prompting breakthrough designation by the FDA.2 Daniel P. Petrylak, MD, presented data on EV-201, the subsequent phase II trial of EV in treatment-refractory locally-advanced or metastatic urothelial cancer.

EV-201 enrolled patients into two cohorts. Cohort 1, which was presented by Dr. Petrylak, enrolled patients who progressed after both anti-PD-1/L1 immunotherapy and platinum-based chemotherapy. Patients in cohort 1 were required to have good performance status (ECOG ≤1) and have no ongoing grade ≥2 sensory neuropathy. A total of 125 patients were treated with EV (1.25 mg/kg on days 1,8, and 15 of a 28 day cycle). The primary endpoint was ORR by RECIST v1.1.


Baseline characteristics were notable for a preponderance of patients with visceral metastases (90%), including 40% of patients with liver metastases, a cohort which has been very challenging to treat. Furthermore, cohort 1 was very heavily pre-treated, with a median of three prior systemic therapies. Although not required for enrolment, nectin-4 expression was identified within the tumors of every single patient.

With respect to the primary outcome, investigators report a noteworthy objective response rate of 44% in this heavily pre-treated poor-prognostic population. Of 125 patients, 15 (12%) achieved a complete response, and an additional 40 (32%) achieved partial responses. Responses were generally identified at first assessment, with a median time to response of 1.8 months and a median duration of response of 7.6 months (range 1.0 – 11.3 months). Cohort 1 achieved a median progression-free survival of 5.8 months and a median overall survival of 11.7 months, which compares very favorably to historical data on platinum-refractory metastatic urothelial cancer.



EV was generally well-tolerated, with only 12% of patients discontinuing for toxicity, most commonly with sensory neuropathy (6%).

Dr. Petrylak notes that, if approved, EV will likely constitute the standard of care in platinum-refractory anti-PD-1/L1 refractory metastatic urothelial cancer; a randomized confirmatory phase III trial, EV-301 is actively enrolling. Furthermore, EV-103 will assess the feasibility of combining EV with anti-PD-1/L1 immunotherapy and/or chemotherapy.  

Presented by: Daniel Peter Petrylak, MD, Medical Oncologist, Professor of Medicine and of Urology, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut, United States

Written by: Michael Lattanzi, MD, Internal Medicine Resident, Department of Medicine, NYU School of Medicine, Twitter: @MikeLattanzi at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, Raitano A, Nadell R, Liu W, Lortie DR, Capo L. Enfortumab vedotin antibody–drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer research. 2016 May 15;76(10):3003-13.
  2. Rosenberg JE, Sridhar SS, Zhang J, Smith DC, Ruether JD, Flaig TW, Baranda JC, Lang JM, Plimack ER, Sangha RS, Heath EI. Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC).
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