Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202.
Antonio Giordano, Arif Awan, Justine Y. Bruce, Hope S. Rugo, Jennifer R. Diamond, Yelena Novik, Joaquina Baranda, Kei Muro, Makiko Ono, Rita Nanda, Jason Kaplan, Seema Rao Gorla, Shubin Liu, Michele Wozniak, Anthony Lee, Tiffany A. Traina
Abstract
1005 Background: EV, a Nectin-4–directed antibody–drug conjugate, is approved for use in urothelial cancer. Nectin-4 is expressed in several solid tumors, including BC. EV monotherapy was evaluated in TNBC and HR+/HER2- BC in EV-202 (NCT04225117). Methods: In this open-label, multicohort, phase 2 trial, eligible adults had locally advanced or metastatic (la/m) solid tumors, measurable disease, and ECOG PS 0–1. In BC cohorts, patients (pts) had prior taxanes or anthracyclines, ≥1 standard-of-care cytotoxic regimen and ≤2 lines (L) of cytotoxic therapy for la/mBC, and prior PD-1/L1 inhibitor (TNBC) or endocrine treatment (tx) with a CDK4/6 inhibitor (HR+/HER2- BC). Nectin-4 expression was not required but was assessed retrospectively. Pts received EV 1.25 mg/kg intravenously days 1, 8, and 15 of each 28-d cycle until discontinuation criteria (eg, disease progression, unacceptable toxicity) were met. Primary endpoint was confirmed objective response rate (ORR); ≥10 (TNBC) or ≥12 (HR+/HER2- BC) responders out of 40 evaluable pts were needed to claim promising antitumor activity. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Antitumor activity was investigator-assessed per RECIST v1.1. Results: In the TNBC cohort, 42 female pts received EV as of Mar 3, 2023 (median follow-up, 11.8 mo). Median age was 53 y, 64% had ≥2L systemic tx for metastatic BC, and 33% had prior sacituzumab govitecan. ORR was 19.0%. Grade ≥3 tx-related adverse events (TRAEs) in >1 pt were decreased neutrophil count (n=3, 7%), decreased white blood cell count (n=2, 5%), and increased aspartate aminotransferase (n=2, 5%). Selected TRAEs of special interest were skin reactions (n=25, 60%), peripheral neuropathy (n=11, 26%), and hyperglycemia (n=2, 5%). In the HR+/HER2- BC cohort (median age, 57.0 y), 45 female pts received EV as of Dec 3, 2022 (median follow-up, 11.2 mo). Most (73%) had ≥3L systemic tx for metastatic BC. ORR was 15.6%. Grade ≥3 TRAEs in >1 pt were maculopapular rash (n=7, 16%), pruritus and increased aspartate aminotransferase (both n=3, 7%), and abdominal pain and erythema (both n=2, 4%). Selected TRAEs of special interest were skin reactions (n=28, 62%), peripheral neuropathy (n=12, 27%), and hyperglycemia (n=5, 11%). Additional efficacy data for both cohorts are in the table. Conclusions: EV showed antitumor activity in heavily pretreated TNBC. Safety in both cohorts was manageable and consistent with previous reports. Clinical trial information: NCT04225117 . [Table: see text]