MP16-09: TRUCE04: A Phase II Clinical Trial of RC48 for High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) (NCT05495724)
Friday, May 3, 2024 1:00 PM to 3:00 PM · 2 hr. (US/Central)
221B
Abstract
Information
Full Abstract and Figures
Author Block
Hailong Hu*, Shizheng Guo, Shiwang Huang, Kaipeng Jia, Peng Li, Chong Shen, Zhe Zhang, Yuanjie Niu, Tianjin, China
Introduction
RC48 is a novel antibody drug conjugate that targets the Her2 protein and has shown promising efficacy in advanced urothelial cancer. However, its efficacy and safety in early-stage urothelial carcinoma are yet to be fully explored. To address this, we conducted a phase II clinical trial to evaluate the value of RC48 in high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
Methods
In this prospective study, 24 patients with Her2-overexpressing (IHC 2+ or 3+) HR-NMIBC who were unable to undergo complete tumor resection or tolerate surgery were enrolled. The pts received either RC48 120mg monotherapy or RC48 120mg combined with tislelizumab 200mg intravenously, once every three weeks, until disease progression, unacceptable toxicity, or study termination. The effectiveness of RC48 was assessed through cystoscopy, random biopsy, urine cytology, and radiological imaging. Complete response (CR) was defined as all assessment results being negative, indicating the absence of any disease. Stable disease (SD) was defined as having at least one positive assessment result, along with a maximum tumor size increase of no more than 20%, while excluding any evidence of muscle-invasive bladder cancer.
Results
All 24 pts completed the efficacy and safety evaluation. The median age of patients was 69 years (range: 58 to 81). Eight pts (33.3%) received RC48 monotherapy, while 16 pts (66.7%) received RC48 combined with tislelizumab. A complete response (CR) was achieved in 16 pts (66.7%,95% CI: 44.7% to 84.4%), and stable disease (SD) in 8 pts (33.3%,95% CI: 15.6 to 55.3%). In 15 pts (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 pts with Her2 IHC 2+, 5 achieved PR, with the PR rate of 55.6% (95% CI: 21.2% to 86.3%). A pt 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.
Conclusions
The results of this study show that both RC48 monotherapy and RC48 combined with tislelizumab have promising efficacy in the treatment of NMIBC. The overall response rate was high, with tolerable and manageable treatment-related adverse events. These findings suggest that RC48 monotherapy and RC48 combined with tislelizumab may be successful strategies for the treatment of NMIBC.
Source Of Funding
The present study was supported by Tianjin Municipal Health Industry Key Project (grant no. TJWJ2022XK014), Scientific Research Project of Tianjin Municipal Education Commission (grant no. 2022ZD069), Tianjin Institute of Urology Talent Funding Program (grant no. MYSRC202310), Clinical Medicine Research Project of the Second Hospital of Tianjin Medical University (grant no. 2023LC03).
Author Block
Hailong Hu*, Shizheng Guo, Shiwang Huang, Kaipeng Jia, Peng Li, Chong Shen, Zhe Zhang, Yuanjie Niu, Tianjin, China
Introduction
RC48 is a novel antibody drug conjugate that targets the Her2 protein and has shown promising efficacy in advanced urothelial cancer. However, its efficacy and safety in early-stage urothelial carcinoma are yet to be fully explored. To address this, we conducted a phase II clinical trial to evaluate the value of RC48 in high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
Methods
In this prospective study, 24 patients with Her2-overexpressing (IHC 2+ or 3+) HR-NMIBC who were unable to undergo complete tumor resection or tolerate surgery were enrolled. The pts received either RC48 120mg monotherapy or RC48 120mg combined with tislelizumab 200mg intravenously, once every three weeks, until disease progression, unacceptable toxicity, or study termination. The effectiveness of RC48 was assessed through cystoscopy, random biopsy, urine cytology, and radiological imaging. Complete response (CR) was defined as all assessment results being negative, indicating the absence of any disease. Stable disease (SD) was defined as having at least one positive assessment result, along with a maximum tumor size increase of no more than 20%, while excluding any evidence of muscle-invasive bladder cancer.
Results
All 24 pts completed the efficacy and safety evaluation. The median age of patients was 69 years (range: 58 to 81). Eight pts (33.3%) received RC48 monotherapy, while 16 pts (66.7%) received RC48 combined with tislelizumab. A complete response (CR) was achieved in 16 pts (66.7%,95% CI: 44.7% to 84.4%), and stable disease (SD) in 8 pts (33.3%,95% CI: 15.6 to 55.3%). In 15 pts (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 pts with Her2 IHC 2+, 5 achieved PR, with the PR rate of 55.6% (95% CI: 21.2% to 86.3%). A pt 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.
Conclusions
The results of this study show that both RC48 monotherapy and RC48 combined with tislelizumab have promising efficacy in the treatment of NMIBC. The overall response rate was high, with tolerable and manageable treatment-related adverse events. These findings suggest that RC48 monotherapy and RC48 combined with tislelizumab may be successful strategies for the treatment of NMIBC.
Source Of Funding
The present study was supported by Tianjin Municipal Health Industry Key Project (grant no. TJWJ2022XK014), Scientific Research Project of Tianjin Municipal Education Commission (grant no. 2022ZD069), Tianjin Institute of Urology Talent Funding Program (grant no. MYSRC202310), Clinical Medicine Research Project of the Second Hospital of Tianjin Medical University (grant no. 2023LC03).