KEY TAKEAWAYS
- The study aimed to investigate the efficacy and safety of RC48 in HR-NMIBC as a novel treatment strategy.
- Researchers noticed that RC48, alone or with tislelizumab, demonstrates promising efficacy and manageable AE’s in patients with NMIBC.
RC48 is a novel antibody-drug conjugate that targets the Her2 protein and has exhibited promising efficacy in advanced urothelial cancer. However, its efficacy and safety in early-stage urothelial carcinoma remain insufficiently explored.
Hailong Hu and the team conducted a phase II clinical trial to assess the potential of RC48 in high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
They performed an inclusive analysis, enrolling 24 patients with Her2-overexpressing (IHC 2+ or 3+) HR-NMIBC who were ineligible for complete tumor resection or surgery. Patients were administered either RC48 120 mg monotherapy or RC48 120 mg combined with tislelizumab 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or study termination.
Effectiveness was evaluated via cystoscopy, random biopsy, urine cytology, and radiological imaging, with complete response (CR) defined as negative results across all assessments indicating the absence of disease and stable disease (SD) characterized by at least 1 positive assessment result with a maximum tumor size increase of ≤20%, excluding evidence of MIBC.
About 24 patients completed the efficacy and safety evaluation. The median age of patients was 69 years (range: 58 to 81). 8 patients (33.3%) received RC48 monotherapy, while 16 patients (66.7%) received RC48 combined with tislelizumab. A CR was achieved in 16 patients (66.7%, 95% CI: 44.7% to 84.4%) and SD in 8 patients (33.3%, 95% CI: 15.6% to 55.3%). In 15 patients (62.5%) with Her2 IHC 3+, 11 achieved PR, with the PR rate of 73.3% (95% CI: 44.9% to 92.2%).
Among the 9 patients with Her2 IHC 2+, 5 achieved PR, with the PR rate of 55.6% (95% CI: 21.2% to 86.3%). A patient died due to non-treatment-related causes. The most commonly reported grade 1-2 treatment-related adverse events (TRAEs) were pruritus (58.3%), rash (41.7%), alopecia (37.5%), and fatigue (37.5%). Grade 3-4 TRAEs were reported in 4 patients (16.7%), including fatigue, pruritus, leukopenia, and neutropenia. No grade 5 adverse events were reported.
The study concluded that both RC48 monotherapy and RC48 combined with tislelizumab have promising efficacy in the treatment of NMIBC. The overall response rate was high, with treatment-related adverse events being tolerable and manageable. These findings suggest that RC48 monotherapy and RC48 combined with tislelizumab may be successful strategies for the treatment of NMIBC.
The study was sponsored by Tianjin Medical University Second Hospital.
Source: https://www.auajournals.org/doi/10.1097/01.JU.0001008640.01272.9d.09
Clinical Trial: https://clinicaltrials.gov/study/NCT05495724
Hu H, Guo S, Huang S, et al. (2024). “TRUCE04: A PHASE II CLINICAL TRIAL OF RC48 FOR HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER (HR-NMIBC) (NCT05495724).” Presented at AUA 2024 (Abstract MP16-09).
