Phase 2 trial of disitamab vedotin plus tislelizumab in transurethrally unresectable, HER2-positive, non-muscle-invasive bladder cancer

Very high-risk non-muscle-invasive bladder cancer (VHR NMIBC) includes extensive high-grade T1 (T1HG) disease, T1HG with carcinoma in situ, variant histology, lymphovascular invasion, or BCG-unresponsive disease. Transurethrally unresectable disease warrants radical cystectomy, but patients ineligible for or declining cystectomy lack established nonsurgical therapy. A phase 2 trial at The Second Hospital of Tianjin Medical University (China) evaluated disitamab vedotin (DV) plus tislelizumab in transurethrally unresectable HER2-positive VHR NMIBC. Patients received an intravenous injection of DV (120 mg, day 1) plus tislelizumab (200 mg, day 2) every 3 weeks for 3 cycles; patients who responded received up to 8 DV cycles and 17 tislelizumab cycles. The primary outcome was complete response (CR) of high-risk disease, defined as no high-grade tumor, T1 disease, carcinoma in situ, of progression. Among 28 participants, two preassessment withdrawals were counted as nonresponders in the all-treated analysis, which left 26 efficacy-evaluable patients CR of high-risk disease was achieved in 19 or 26 participants (73.1%; 95% CI 54.8-91.3), meeting the prespecified 70% alternative-rate goal. The figure shows duration of response and survival outcomes. Among responders, the 24-month sustained response was 83.5% (95% CI 68.0-100), and no muscle-invasive or metastatic progression occurred. Treatment-related adverse events occurred in 89.3%; grade 3 to 4 events in 14.3%; discontinuation in 7.1%; and grade 5 events in none. The authors conclude that these findings suggest that DV plus tislelizumab may show a high CR rate and durable disease control in patients with transurethrally unresectable HER2-positive VHR NMIBC.