A COMBINATION of disitamab vedotin and tislelizumab achieved a 73.1% complete response rate in patients with transurethrally unresectable, ERBB2-positive, very high-risk non-muscle-invasive bladder cancer (VHR NMIBC), with responses sustained at 24 months in most responders. The findings from a phase II nonrandomised clinical trial suggest that the investigational regimen could offer a nonsurgical treatment option for patients unable or unwilling to undergo radical cystectomy.
The open-label study enrolled 28 adults at an academic hospital between August 2022 and May 2024, with a median follow-up of 29.4 months. Participants had very high-risk disease and were ineligible for or declined cystectomy. Treatment combined disitamab vedotin, an anti-ERBB2 antibody-drug conjugate, with tislelizumab, an immune checkpoint inhibitor targeting programmed cell death protein 1.
Patients received three cycles of both agents, administered intravenously every three weeks. Responders could continue treatment for up to eight cycles of disitamab vedotin and 17 cycles of tislelizumab.
Among the 26 patients evaluable for efficacy, 19 achieved a complete response of high-risk disease (73.1%; 95% confidence interval [CI]: 54.8–91.3%), meeting the prespecified response target of 70%. In the analysis of all 28 treated participants, 19 responded, equivalent to 67.9% (95% CI: 49.4–86.3%).
Among responders, the estimated sustained response rate at 24 months was 83.5% (95% CI: 68.0–100.0%). No progression to muscle-invasive or metastatic disease was observed during follow-up, suggesting durable disease control in this cohort.
Treatment-related adverse events occurred in 25 participants (89.3%). The most common were paraesthesia in 12 patients (42.9%), alopecia in 11 (39.3%), and pruritus in 10 (35.7%). Four participants (14.3%) experienced grade 3–4 treatment-related adverse events, while two (7.1%) discontinued treatment. No grade 5 treatment-related adverse events were reported.
The authors concluded that the combination showed promising response rates and durable disease control in this difficult-to-treat population. However, the study was small, single-arm and nonrandomised, limiting comparisons with other treatments. The findings support further evaluation in randomised clinical trials to establish the regimen’s efficacy and safety and clarify its potential role for patients with unresectable, ERBB2-positive VHR NMIBC.
Reference
Qie Y et al. Disitamab vedotin plus tislelizumab in transurethrally unresectable, ERBB2-positive, non–muscle-invasive bladder cancer: a nonrandomized clinical trial. JAMA Oncol. 2026;DOI:10.1001/jamaoncol.2026.3909.
Featured image: Maria Vitkovska on Adobe Stock
Featured image: Maria Vitkovska on Adobe Stock
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