Phase II trial of intravesical camrelizumab in BCG-unresponsive high-risk non-muscle invasive bladder cancer.

4594 Background: In a phase I study, intravesical camrelizumab (at a maximum tolerated dose MTD of 200 mg) was well tolerated by patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC). This phase II trial aimed to assess the efficacy and safety of intravesical camrelizumab at the established phase I MTD. Methods: Patients with histologically confirmed BCG-unresponsive high-risk NMIBC, who were ineligible for or declined radical cystectomy, received intravesical camrelizumab at a dose of 200 mg every week for up to 6 weeks as the induction course. Subsequently, the maintenance therapy started with 200 mg administered every 3 weeks and continued until reaching the maximum treatment duration of 2 years or in the event of disease progression or unacceptable toxicity. The primary endpoint was the 3-month event-free survival (EFS) rate. The secondary endpoints included 6-month EFS rate, 1-year EFS rate, recurrence-free survival (RFS), progression-free survival (PFS), and safety. Biomarker exploration included PD-L1 expression and protein sequencing. Results: Between June 2021, and December 2023, 14 patients were enrolled and received at least one dose of camrelizumab, all of whom were included in the safety analysis.At a median follow-up of 23.1 months (IQR 15.8-28.6), the median EFS was 12.68 months (95% CI 6.31-NE), with a 3-month EFS rate of 92.3% (95%CI 77.8-100), a 6-month EFS rate of 75.5% (95%CI 51.4-99.7) and a 12-month EFS rate of 50.3% (95%CI 22.1-78.6). Both median RFS and PFS was 12.68 months (95% CI 6.31-NE). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 2 (14.3%) patients, one with urinary tract infection and the other with vertebrobasilar insufficiency. Serious TEAEs occurred in one (7.1%) patient. No deaths were reported. PD-L1 expression was not related to treatment efficacy. Protein sequencing revealed a total of 296 proteins with differential expression between responsive and unresponsive patients. Analysis using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that the responsive group was associated with activated biological processes, including T cell receptor signaling pathway, alpha-beta T cell activation, and adaptive immune response. Conclusions: Intravesical camrelizumab demonstrated promising anti-tumor activity and acceptable tolerance in patients with BCG-unresponsive NMIBC who either declined or were ineligible for radical cystectomy. This suggests its potential as an effective non-surgical and topical treatment option for this specific population. The efficacy was attributed to enhanced immune pathway activation. Clinical trial information: NCT04706598 .