Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202.

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