Treatment with the anti-ERBB2 antibody-drug conjugate disitamab vedotin plus the anti–PD-1 immune checkpoint inhibitor tislelizumab-jsgr showed evidence of antitumor activity in patients with transurethrally unresectable, ERBB2-positive, very high–risk non–muscle invasive bladder cancer, according to findings from a single-arm phase II trial published by Qie et al in JAMA Oncology.
“The observed [complete response] rate and durable disease control support further evaluation of this [antibody-drug conjugate/immune checkpoint inhibitor] combination therapy in larger, multicenter randomized clinical trials to assess its efficacy and long-term clinical benefit,” the investigators wrote.
Study Details
The nonrandomized trial used a Simon’s two-stage design and was conducted at a single academic hospital from August 2022 to May 2024. A total of 28 adults with transurethrally unresectable ERBB2-positive non–muscle invasive bladder cancer who met the 2019 European Association of Urology criteria for very high–risk disease and were ineligible for or declined cystectomy were included. The median age was 72 years, 25 patients (89%) were male, and median follow-up was 29.4 months.
Patients were treated with 120 mg of intravenous disitamab vedotin on day 1 and 200 mg of tislelizumab on day 2 every 3 weeks for 3 cycles, with responders eligible for up to 8 and 17 cycles, respectively.
The primary endpoint was complete response of high-risk disease, requiring no evidence of high-grade tumors, stage T1 disease, carcinoma in situ, or disease progression. Duration of response, progression-free survival, overall survival, and safety were evaluated as secondary endpoints. Two patients withdrew before response assessment and were counted as nonresponders in the all-treated analysis.
Key Findings
Complete responses of high-risk disease were observed in 73.1% of the efficacy-evaluable population (19 of 26 patients; 95% confidence interval [CI] = 54.8%–91.3%), exceeding the prespecified alternative-rate target of 70%. The response rate in the all-treated population was 67.9% (19 of 28 patients; 95% CI = 49.4%–86.3%); this surpassed the exact binomial threshold of 17 responses. The investigators reported that the primary criterion was met in both analyses.
Responses were sustained at 24 months in 83.5% of responders (95% CI = 68.0%–100.0%), and no cases of muscle-invasive or metastatic progression were observed.
Treatment-related adverse events were reported in 25 patients (89.3%), most frequently paresthesia (42.9%), alopecia (39.3%), and pruritus (35.7%). Grade 3 or 4 events occurred in four patients (14.3%), and two (7.1%) discontinued treatment because of them. No grade 5 events were reported.
“Findings of this nonrandomized clinical trial suggest that [disitamab vedotin] plus tislelizumab may show a high [complete response] rate and durable disease control in patients with transurethrally unresectable, ERBB2-positive, [very high–risk non–muscle-invasive bladder cancer], supporting randomized clinical trials,” the investigators concluded.
Hailong Hu, MD, and Chong Shen, MD, of Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, China, are the corresponding authors of the article in JAMA Oncology.
DISCLOSURE: The study was supported by awards from the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, National Key R&D Program of China, Joint Funds of the Natural Science Foundation of Tianjin, and the Tianjin Municipal Medical Key Discipline Construction Project. The study authors reported no conflicts of interest.
