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8585 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 NSCLC. EV monotherapy was evaluated in non-squamous and squamous NSCLC cohorts in EV-202 (NCT04225117). Methods: This open-label, multicohort, phase 2 trial enrolled adults with locally advanced or metastatic solid tumors and ECOG PS 0–1. For NSCLC cohorts, patients (pts) had NSCLC not amenable to curative-intent treatment (tx), 1 platinum-based and ≤2 lines of cytotoxic tx for locally advanced or metastatic NSCLC, and prior PD-1/L1 inhibitor unless contraindicated. Nectin-4 expression was not required for inclusion but was assessed retrospectively. Pts received EV 1.25 mg/kg intravenously on days 1, 8, and 15 of each 28-d cycle until discontinuation. Interim analysis (IA) was conducted for each cohort when 20 pts were response-evaluable. If the cohort-specific minimum number of responders (non-squamous: 3; squamous: 2) was not met, enrollment could be closed. Primary endpoint was confirmed objective response rate (ORR). 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: The non-squamous cohort met the minimum number of responders at IA and continued enrollment. Of 43 pts in this cohort as of Feb 21, 2022, median age was 67 y (range, 36–82), 51% were male, and 47% had ≥3 prior lines of systemic tx. Histology at diagnosis was adenocarcinoma for 38 (88%) pts. Efficacy and overall tx-related adverse event (TRAE) data are in the table. Common TRAEs in the non-squamous cohort were maculopapular rash and peripheral sensory neuropathy (both n=16, 37%), pruritus (n=15, 35%), and alopecia (n=14, 33%). Grade ≥3 TRAEs in >1 pt were maculopapular rash (n=3, 7%) and decreased neutrophil count (n=2, 5%). Selected TRAEs of special interest were skin reactions (n=24, 56%), peripheral neuropathy (n=16, 37%), and hyperglycemia (n=3, 7%). Only 1 of 20 pts in the squamous cohort had achieved a response at IA; thus, enrollment closed. The table shows data from the primary analysis (Jul 15, 2022; N=23). Conclusions: EV showed antitumor activity in heavily pretreated non-squamous NSCLC and manageable safety consistent with the known safety profile. The IA efficacy threshold was not met in squamous NSCLC. Clinical trial information: NCT04225117 . Table: see text
Muro et al. (Sat,) studied this question.