EV-302: Long-term subgroup analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

4571 Background: EV-302/KEYNOTE-A39 (NCT04223856) demonstrated superior efficacy of first-line (1L) EV+P vs chemo and established EV+P as the standard of care (SOC). EV+P is included in global treatment guidelines for patients (pts) with untreated la/mUC. After ≈2.5 years of median follow-up, the benefit of EV+P was sustained; median OS was maintained for > 2.5 years. We present long-term efficacy and safety analyses in the following prespecified subgroups: primary disease site of origin (upper and lower tracts), lymph node (LN)–only disease, and presence of liver metastases (mets) (present and absent). Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 and 8; IV) and P (200 mg; Day 1; IV) or chemo (gemcitabine with cisplatin or carboplatin) every 3 wk. Primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). A genAI tool (01/09/25; Pfizer; GPT-4o) developed the 1 st draft; authors assume content responsibility. Results: Pts (N = 886) were randomized to receive EV+P (n = 442) or chemo (n = 444) and were analyzed according to the subgroups shown in the Table. At data cutoff (Aug 8, 2024), median follow-up was 29.1 mo (95% CI, 28.5-29.9). PFS by BICR, OS, duration of response, and objective response rate continued to demonstrate sustained benefit of EV+P vs chemo across prespecified subgroups after long-term follow-up (Table). For EV+P, treatment-related adverse events (TRAEs) occurred in 96.0-98.5% and Grade ≥3 TRAEs in 53.4-60.7% of pts across prespecified subgroups, generally consistent with previous reports. Conclusions: EV+P continues to demonstrate superior long-term efficacy vs chemo in key subgroups with both favorable and poor prognoses. There were no new safety signals, and AE rates in prespecified subgroups were consistent with the overall population after an additional year of follow-up. This reinforces EV+P as the SOC for the 1L treatment of pts with la/mUC. Clinical trial information: NCT04223856 . Upper tract Lower tract LN only Liver mets present Liver mets absent EV+P, n (%) 135 (30.5) 305 (69.0) 103 (23.3) 100 (22.6) 342 (77.4) Chemo, n (%) 104 (23.4) 339 (76.4) 104 (23.4) 99 (22.3) 345 (77.7) mPFS, moEV+P 12.3 12.8 22.1 8.1 16.4 Chemo 6.2 6.3 8.3 6.0 6.4 PFS HR (95% CI) 0.542 (0.384-0.763) 0.462(0.379-0.564) 0.473 (0.317-0.704) 0.548 (0.392-0.766) 0.458 (0.376-0.557) mOS, moEV+P 36.5 32.9 NR 19.1 39.3 Chemo 18.3 15.6 24.4 10.1 18.3 OS HR(95% CI) 0.538 (0.371-0.781) 0.504 (0.408-0.623) 0.512 (0.332-0.789) 0.556 (0.399-0.776) 0.496 (0.400-0.615)