Disitamab Vedotin Plus Toripalimab Shows Promise as Neoadjuvant Therapy in HER2-Expressing MIBC

At the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium, updated results of the single-arm phase II RC48-C017 trial were presented, which evaluated the efficacy and safety of neoadjuvant disitamab vedotin (DV) with perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression. Data from the study’s post hoc event-free survival (EFS) analysis were also presented.

Preliminary results of the study showed promising efficacy and acceptable safety with neoadjuvant treatment with DV plus toripalimab in patients with HER2-expressing MIBC.

A total of 47 patients with previously untreated MIBC (cT2-4aN0-1M0) with HER2 expression (immunohistochemistry [IHC] ≥1+ by local test) were enrolled and treated in the study. Each patient was eligible for radical cystectomy and pelvic lymph node dissection (RC+PLND) with curative intent.

Patients were administered DV, 2 mg/kg, with toripalimab, 3 mg/kg, every two weeks for six cycles during the neoadjuvant phase. After undergoing PC+PLND, patients were given adjuvant toripalimab at 3 mg/kg every two weeks for up to 20 cycles.

The primary endpoint of the study was pathologic complete response (pCR) rate (ypT0N0) assessed by the investigators. Secondary endpoints included pathologic response rate (PRR, ≤ypT1N0M0), overall survival, and safety.

As of the data cutoff date of September 2024, RC+PLND was performed in 33 (70.2%) patients. The pCR rate was 63.6% (95% CI, 45.1%-79.6%), and the PRR was 75.8% (95% CI, 57.7%-88.9%). A higher pCR rate of 84.6% was observed among patients with HER2 IHC 3+.

The pCR rate was 77.8% in the PD-L1–positive subgroup and 62.5% in the PD-L1–negative subgroup. The 1-year EFS rate was 89.5% (95% CI, 69.8%-96.7%). The safety profile aligned with previous findings, with no new toxicity signals observed. No adverse events led to delays in surgery, and survival data remain immature.

This updated data from the RC48-C017 trial support the use of perioperative treatment with DV plus toripalimab, demonstrating promising safety and efficacy results in patients with HER2-expressing MIBC.