Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

4502 Background: EV-302/KEYNOTE-A39 (NCT04223856) showed significant PFS and OS benefits for pts with previously untreated la/mUC treated with EV+P vs chemo, which established EV+P as the SOC in this population. This exploratory analysis presents efficacy and safety results for responders, focusing on pts with confirmed complete response (cCR). Methods: Pts were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 and 8; IV) + P (200 mg; Day 1; IV) or chemo (gemcitabine + cisplatin/carboplatin); all Q3W. Primary endpoints were PFS by BICR and OS. Secondary endpoints included ORR, DOR, and safety. An exploratory analysis evaluated outcomes in pts with cCR. A genAI tool (01/09/25; Pfizer; GPT-4o) developed the 1 st draft; authors assume content responsibility. Results: Median follow-up (data cutoff: Aug 8, 2024) was 29.1 mo (95% CI, 28.5-29.9). 886 pts were randomized to EV+P (n = 442) vs chemo (n = 444). Confirmed ORR (CR+PR) was 67.5% with EV+P and 44.2% with chemo; cCR was 30.4% and 14.5%, respectively. Baseline characteristics of responders were generally consistent with the ITT population. Among pts with cCR in the EV+P arm, 38 (28.6%) had upper tract disease and 20 (15%) had liver metastases. For pts with cCR, mPFS by BICR was not reached (NR) with EV+P and 26.9 mo with chemo (HR, 0.36; 95% CI, 0.21-0.61); mOS was NR with both EV+P and chemo (HR, 0.37; 95% CI, 0.17-0.80). Median duration of CR was NR for EV+P and 15.2 mo for chemo. Efficacy data are in the Table. Among pts with cCR in the EV+P arm, the median number of cycles was 13 (range, 1-50) for EV and 27 (range, 1-35) for P; median treatment (tx) duration was 22.0 mo (range, 0.7-35.4). Safety among responders was generally consistent with previous reports. TRAEs leading to dose modification in pts with cCR are in the Table. Grade ≥3 TRAEs occurred in 61.7% and 71.9% of pts with cCR in the EV+P and chemo arms, respectively. EV tx-related AESIs and P tx-emergent AEOSI profiles were generally consistent with previous reports. There were no tx-related deaths among pts with cCR. Conclusions: In the EV+P arm, the proportion of pts achieving cCR was twice that in the chemo arm. Consistent with the ITT data, EV+P reduced the risk of progression or death vs chemo in pts achieving cCR, with appropriate dose modifications. These data reinforce EV+P as the SOC for 1L tx of pts with la/mUC. Clinical trial information: NCT04223856 . EV+PcCR: n=133 ChemocCR: n=64 Median PFS, mo (95% CI) NR (NE-NE) 26.9 (16.6-NE) 24-mo PFS rate, % (95% CI) 78.2 (69.8-84.6) 53.7 (40.0-65.5) Median OS, mo (95% CI) NR (39.3-NE) NR (32.1-NE) 24-mo OS rate, % (95% CI) 95.4 (90.0-97.9) 85.8 (74.6-92.4) Median DOCR, mo (95% CI) NR (NE-NE) 15.2 (10.3-NE) 24-mo cCR rate, % (95% CI) 74.3 (65.1-81.4) 43.2 (28.7-56.9) TRAEs leading to dose modification (n, %)Dose interruption of EVDose reduction of EVDose interruption of P 94 (70.7)86 (64.7)86 (64.7) ---