Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression: Updated efficacy and safety results from the phase II RC48-C017 trial.

665 Background: This single-arm phase II trial was conducted to evaluate the efficacy and safety of neoadjuvent disitamab vedotin (DV, a HER2-targetted monoclonal antibody conjugated with monomethyl auristatin E) plus perioperative toripalimab (an anti-PD-1 inhibitor) in MIBC patients (pts) with HER2 expression. The preliminary results showed promising efficacy and acceptable safety with neoadjuvant treatment with DV plus toripalimab in pts with HER2-expressing MIBC (Sheng, et al. ASCO Annual meeting 2024). Methods: Key eligibility criteria included previously untreated MIBC (cT2-4aN0-1M0) with HER2 expression (immunohistochemistry [IHC] ≥1+ by local test), and eligible for curative-intent radical cystectomy and pelvic lymph node dissection (RC+PLND). Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every 2 weeks for 6 cycles at neoadjuvant phase. After RC+PLND, pts received adjuvant toripalimab (3 mg/kg every 2 weeks) for up to 20 cycles. The primary endpoint was pathological complete response (pCR, ypT0N0) rate assessed by the investigators; secondary endpoints included pathological response rate (≤ypT1N0M0), overall survival, safety, etc. Here we present the updated efficacy and safety results and post-hoc event-free survival (EFS) analysis with data cutoff date (DCO) of September, 2024. Results: As of DCO, patient enrollment was completed with 47 pts enrolled and treated (including 10.6% pts with HER2 IHC 1+, 57.4% IHC 2+, and 31.9% IHC 3+; 83.0% pts at baseline T2-4N0M0 and 17.0% at cT2-4aN1M0 stage). RC+PLND was performed in 33 (70.2%) pts. The pCR rate was 63.6% (95% CI: 45.1%-79.6%) and the pathological response rate was 75.8% (95% CI: 57.7%-88.9%). A higher pCR rate of 84.6% was observed in patients with HER2 IHC 3+. The pCR rate was 77.8% and 62.5% in PD-L1-positive and PD-L1-negative subgroups, respectively. The one-year EFS rate was 89.5% (95% CI: 69.8%-96.7%). The safety profile was consistent with the previous ASCO presentation without new toxicity signals observed. No adverse events delayed the surgery. Survival data were immature. Conclusions: The updated data supported perioperative treatment with DV plus toripalimab had promising efficacy and acceptable safety in pts with HER2-expressing MIBC. It warrants further investigation in this patient population. Clinical trial information: NCT05297552 .