NCT05016973

A Clinical Study of RC48-ADC Combined With Triplizumab For Treatment of Myometrial Invasive Bladder Cancer

A Clinical Study of RC48-ADC Combined With Triplizumab as Neoadjuvant Therapy Before Radical Resection of Myometrial Invasive Bladder Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this project is to explore whether Monoclonal Antibody-MMAE Conjugate for Injection (RC48-ADC) combined with Triplizumab as a preoperative neoadjuvant therapy for myometrial invasive bladder cancer (MIBC) can achieve a good tumor descending period, so as to prolong disease-free survival and overall survival.

Detailed description

Bladder cancer is the most common malignant tumor of the urinary system, mainly urothelial cancer, and its morbidity and mortality are increasing year by year. According to cancer statistics published by CACancerJClin, there were about 81000 new cases of bladder cancer in China in 2015, and the number of deaths from bladder cancer reached 33000. According to the depth of invasion, bladder cancer can be divided into superficial bladder cancer and muscular invasive bladder cancer. More than 70% of superficial bladder cancers recur after initial treatment, and about 15% eventually develop into invasive cancer. The prognosis of superficial bladder cancer is good (the 5-year survival rate is more than 90%). After entering the stage of myometrial invasion, the 5-year survival rate is only 60%, while the 5-year survival rate of patients with local advanced stage or metastasis is less than 15%. Bladder cancer has been shown to be sensitive to chemotherapeutic drugs such as platinum, gemcitabine, doxorubicin and taxanes. The results show that in the stage of localized myometrial invasive bladder cancer, cisplatin-based neoadjuvant chemotherapy can significantly improve the median survival time of patients with myometrial invasive bladder cancer up to 31 months, showing a significant survival advantage. Therefore, neoadjuvant chemotherapy is routinely recommended before radical resection for bladder cancer patients who can tolerate cisplatin. However, a single neoadjuvant chemotherapy can not meet the needs of all bladder cancer patients, so it is necessary to find new treatments to further supplement or improve the traditional neoadjuvant chemotherapy, so as to improve the postoperative survival of patients. Since 2020, our group has also carried out a phase II clinical study of Tripril combined with GC regimen as a neoadjuvant regimen before MIBC. Triplet monoclonal antibody injection (Tuoyi) is a new type of recombinant humanized anti-PD-1 monoclonal antibody independently developed in China. At present, 18 cases have been enrolled in the study, 13 cases have been completed, and the rate of PaR and 31% pCR has reached 69.2%. The effect is similar to that of similar studies abroad. In spite of this, the combined therapy of immunity and chemotherapy is limited by the strong toxicity of platinum drugs, and some patients are still unable to tolerate it. In recent years, the emergence of antibody drug conjugates (antibody-drugconjugate,ADC) provides a new choice for these patients. Studies have shown that ADC drugs and ICI drugs are highly complementary and safe. In addition, according to the results of the EV103 study, it can be found that the combination of ADC and ICI has a significant synergistic effect and has a strong and rapid shrinking effect on urothelial cancer. At the same time, these two drugs do not require high renal function, so they are very suitable for neoadjuvant therapy before MIBC. RC48-ADC (Recombinant humanized Anti-HER2 Monoclonal Antibody-MMAE Coupling Agent for injection, referred to as RC48-ADC) independently developed by Rongchang Biopharmaceuticals in China is the first clinically approved HER2 antibody coupling drug in China. RC48-ADC exerts its anti-tumor effect through two main pathways: one is to interfere with cell transcription, growth and proliferation by inhibiting downstream signal pathways activated by HER2 (such as PI3K/AKT), and the other is the interference of microtubule formation by small molecule MMAE, which is mainly manifested by depolymerizing microtubules and inducing cell cycle arrest in G2max M phase. In addition, in vitro studies have shown that RC48-ADC has a tumor inhibitory effect on HER2 overexpressed cancer cells through antibody-dependent cell-mediated cytotoxicity (ADCC). About 25-30% of bladder cancers show high expression of HER2, and these tumors tend to have higher stage and grade, are more prone to invasion and metastasis and have a poor prognosis. Therefore, RC48-ADC has a high application prospect in bladder cancer with high expression of HER2. The RC48-C005 study is a single-arm, open, multicenter II phase clinical study in China to evaluate RC48-ADC in the treatment of locally advanced or metastatic bladder urothelial carcinoma with overexpression of HER2. Through this study, it can be found that RC48-ADC has significant therapeutic efficacy and good safety in advanced urothelial cancer with high expression of Her-2. Based on this, this study intend to use the combination of ADC drugs and ICI drugs (RC48-ADC combined with triplizumab) as preoperative neoadjuvant therapy for patients with high expression of MIBC in HER2, in order to achieve a better effect of tumor decline, so as to prolong the disease-free survival and overall survival of patients.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	RC48-ADC	2.0mg/kg, Intravenous drip on days 1 every 21 days
DRUG	Triplizumab	240mg, Intravenous drip on days 1 every 21 days

Timeline

• Start date: 2021-10-01
• Primary completion: 2024-09-01
• Completion: 2024-10-01
• First posted: 2021-08-23
• Last updated: 2021-08-23

Locations

1 site across 1 country: China