Enfortumab vedotin in patients with advanced non-small cell lung cancer after disease progression on platinum- and PD-1/PD-L1 inhibitor-containing regimens: Phase 2 international multicenter EV-202 study

Purpose: Enfortumab vedotin (EV), a novel antibody–drug conjugate directed against Nectin-4, was explored in patients with non-small cell lung cancer (NSCLC) in cohorts 3 and 4 of the open-label, multicohort, Phase 2 EV-202 study (NCT04225117). Methods: Patients with squamous and non-squamous NSCLC previously treated with platinum and PD-1/L1 inhibitors received EV 1.25 mg/kg intravenously on days 1, 8, and 15 of 28-day cycles. A Bayesian optimal design for Phase 2 was used, with interim analysis (IA) conducted when 20 patients were response-evaluable by investigator assessment. Primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Of 40 patients, ≥ 7 and ≥ 10 responders were needed at final analysis to claim promising antitumor activity in squamous and non-squamous cohorts, respectively. Results: Sixty-six patients were enrolled: 23 in squamous, 43 in the non-squamous cohort. One patient in the squamous cohort achieved a response at IA; thus, enrollment was closed. In the non-squamous cohort, 6 patients achieved partial response (ORR [95 % CI], 14.0 % [5.3–27.9 %]) at final analysis; median (95 % CI) PFS and OS were 4.1 (2.8–5.7) and 10.5 (8.1–13.1) months, respectively. Most common treatment-related adverse events (≥30 % patients) in the non-squamous cohort were rash maculopapular and peripheral sensory neuropathy (37.2 % each); pruritus (34.9 %); and alopecia (32.6 %). Conclusions: Although the predefined efficacy thresholds were not met in either cohort, the antitumor activity of EV in non-squamous NSCLC may support the option for further investigation in this population.