Study EV-103 cohort H: Neoadjuvant treatment with enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) with muscle invasive bladder cancer (MIBC)—3-year efficacy results.

4583 Background: For cis-ineligible pts with MIBC undergoing radical cystectomy and pelvic lymph node dissection (RC+PLND), no neoadjuvant treatment options have been shown to improve survival, highlighting a clinical need. EV previously demonstrated encouraging antitumor activity in cis-ineligible pts with MIBC as neoadjuvant treatment in EV-103 Cohort H. We present updated 3-year efficacy results. Methods: EV-103 Cohort H enrolled cis-ineligible pts with MIBC (cT2-T4aN0M0) and ECOG PS ≤2 who were eligible for RC+PLND. Pts received neoadjuvant EV monotherapy (1.25 mg/kg) on Days 1 and 8 every 21 days for 3 cycles before undergoing RC+PLND. Primary endpoint was pathological complete response (pCR) rate by central pathology review. Secondary endpoints included event-free survival (EFS) per investigator assessment (INV), OS, and safety. A genAI tool (01/09/25; Pfizer; GPT-4o) developed the 1 st draft; authors assume content responsibility. Results: Overall, 22 pts were enrolled. 86.4% of pts completed all 3 cycles of neoadjuvant EV treatment. Three pts (13.6%) discontinued neoadjuvant EV due to AEs. All pts underwent RC+PLND; 13 (59.1%) were in long-term follow-up at data cutoff (Nov 20, 2024). Median follow-up was 49.7 mo (range, 3.1-53.6). pCR rate was 36.4% (8/22; 95% CI, 17.2-59.3). Median EFS by INV was 40.1 mo (95% CI, 14.5-NE) for all pts, NR (95% CI, 6.5-NE) for pts with pCR, and 18.8 mo (95% CI, 6.7-NE) for pts without pCR. Estimated EFS rate by INV at 24 and 36 months was 62.0% (95% CI, 38.2-78.9) and 56.9% (95% CI, 33.4-74.8), respectively, and improved in pts with pCR. Median OS was NR (95% CI, 33.4-NE) in all pts. Estimated OS rate at 24 and 36 months was 77.3% (95% CI, 53.7-89.9) and 68.2% (95% CI, 44.6-83.4), respectively. Key updated 3-year efficacy data are shown in the Table. The safety profile was consistent with prior reports, and no new safety concerns were seen. Conclusions: Based on 3-year efficacy results, neoadjuvant EV monotherapy treatment continued to show encouraging antitumor activity in cis-ineligible pts with MIBC, including median EFS and OS exceeding historical real-world data in cis-ineligible patients following RC alone (Li Eur Urol Oncol 2024; Rose SESAUA 2023). The safety profile was generally manageable and consistent with the known AE profile of EV in other settings. Phase 3 trials evaluating perioperative EV + pembrolizumab in cis-eligible and -ineligible pts with MIBC (KN-905/EV-303, KN-B15/EV-304) are ongoing. Clinical trial information: NCT03288545 . Median EFS by INV (95% CI), monthsAll ptspCRNon-pCR 40.1 (14.5-NE)NR (6.5-NE)18.8 (6.7-NE) 3-year EFS rate by INV (95% CI), %All ptspCRNon-pCR 56.9 (33.4-74.8)72.9 (27.6-92.5)46.4 (19.3-69.9) Median OS (95% CI), months NR (33.4-NE) 3-year OS rate (95% CI), % 68.2 (44.6-83.4) n=22. Median values should be interpreted with caution due to small sample size.