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EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors.

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Balar, AV; McGregor, BA; Rosenberg, JE; Van Der Heijden, MS; Park, SH; Lee, J-L; Harrison, MR; Heath, EI; Stein, MN; Loriot, Y; Necchi, A ...
Published in: Journal of Clinical Oncology
February 20, 2021

394 Background: Cisplatin (cis)-ineligible, platinum-naive patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) who progress on/after PD-1/L1 inhibitors (PD-1/L1-i) have a poor prognosis and few treatment (tx) options. Enfortumab vedotin (EV) is an antibody-drug conjugate directed against Nectin-4, an immunoglobulin-like cell adhesion molecule highly expressed in UC. EV-201 (NCT03219333) is a pivotal, single-arm, 2-cohort study of EV in la/mUC; Cohort (C) 1 data led to FDA accelerated approval of EV in adult pts with la/mUC who previously received a PD-1/L1-i and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, la/mUC setting. Here, we present the primary analysis from C2: cis-ineligible pts with prior PD-1/L1-i and no prior platinum for la/mUC. Methods: Pts in this open-label, multicenter, multinational study received 1.25 mg/kg EV on Days 1, 8, and 15 of each 28-day cycle. Primary endpoint was confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of 08 Sep 2020 (data cutoff), 91 pts were enrolled and 89 treated in C2. Pts were elderly (median age: 75 y [range: 49-90]) with comorbidities, including moderate/severe renal impairment. Pts were cis-ineligible at study entry due to CrCl < 60 mL/min (66%), Grade ≥2 hearing loss (15%), or ECOG PS 2 (7%); an additional 12% met ≥1 criterion. The primary tumor site was in upper tract in 43%; 79% had visceral mets, including 24% with liver mets. Median (m) tx duration was 6.0 mo (range: 0.3 – 24.6). Confirmed ORR per BICR was 52% (95% CI: 40.8–62.4), including 20% CR among treated pts. mDOR was 10.9 mo (95% CI: 5.8–NR). mPFS and mOS were 5.8 mo (95% CI 5.0-8.3) and 14.7 mo (95% CI 10.5-18.2), respectively. Most common all-grade tx-related AEs were alopecia (51%), peripheral sensory neuropathy (47%), and fatigue (34%). Tx-related AEs of interest included rash (61% all grade, 17% ≥G3), peripheral neuropathy (54% all grade, 8% ≥G3), and hyperglycemia (10% all grade, 6% ≥G3). Four deaths were reported as tx related by investigators, all in pts ≥75 y with multiple comorbidities: 3 events ≤30 d of first EV dose in pts with BMI ≥30(acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome) and 1 event > 30 d after last dose (pneumonitis). Conclusions: In EV-201 C2, the majority of platinum-naive, cis-ineligible la/mUC pts who progressed on/after PD-1/L1-i achieved durable responses to EV, with 1/5 achieving CR. PFS and OS were encouraging. Safety was consistent with the previously reported AE profile of EV, within the context of a patient population with advanced malignancy and comorbidity. These data show the potential for EV as a non-platinum option following PD-1/L1-i. Clinical trial information: NCT03219333.

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Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

394 / 394

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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Balar, A. V., McGregor, B. A., Rosenberg, J. E., Van Der Heijden, M. S., Park, S. H., Lee, J.-L., … Yu, E. Y. (2021). EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. In Journal of Clinical Oncology (Vol. 39, pp. 394–394). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.6_suppl.394
Balar, Arjun Vasant, Bradley Alexander McGregor, Jonathan E. Rosenberg, Michiel Simon Van Der Heijden, Se Hoon Park, Jae-Lyun Lee, Michael Roger Harrison, et al. “EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors.” In Journal of Clinical Oncology, 39:394–394. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.6_suppl.394.
Balar AV, McGregor BA, Rosenberg JE, Van Der Heijden MS, Park SH, Lee J-L, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 394–394.
Balar, Arjun Vasant, et al. “EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 394–394. Crossref, doi:10.1200/jco.2021.39.6_suppl.394.
Balar AV, McGregor BA, Rosenberg JE, Van Der Heijden MS, Park SH, Lee J-L, Harrison MR, Heath EI, Stein MN, Loriot Y, Necchi A, Steinberg JL, Liang S-Y, Kim E, Trowbridge J, Campbell MS, Petrylak DP, Yu EY. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 394–394.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

394 / 394

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences