Propranolol With Tislelizumab Plus GC in Neoadjuvant Bladder UC

Summary

This is a prospective, multicenter, Phase Ib clinical study designed to evaluate the safety and preliminary efficacy of propranolol combined with tislelizumab plus gemcitabine/cisplatin (GC) as neoadjuvant therapy for patients with bladder urothelial carcinoma with clinical lymph node involvement (cT1-T4aN1-3M0). Current neoadjuvant immunochemotherapy regimens can improve clinical outcomes in cisplatin-eligible patients; however, patients with lymph node metastasis show a significantly poorer pathological complete response (pCR) rate compared with non-metastatic cases. Real-world clinical observations have shown that more than 20% of patients achieve complete response in the primary tumor after immunotherapy but have persistent or progressive positive lymph nodes, suggesting unique resistance mechanisms within lymph node metastatic lesions.

Preclinical studies conducted by our team demonstrated that sympathetic innervation within lymph nodes releases norepinephrine, which activates β-adrenergic signaling in metastatic tumor cells and promotes lipid metabolic reprogramming, leading to CD8⁺ T-cell exhaustion and immune resistance. Propranolol, a non-selective β-adrenergic blocker, may reduce metabolic stress and restore antitumor immunity, potentially enhancing the efficacy of immune checkpoint blockade.

In this study, enrolled patients will receive oral propranolol in combination with intravenous tislelizumab and standard GC chemotherapy prior to surgery. Participants will be closely monitored for treatment-related adverse events, including cardiovascular events, hematologic toxicity, and immune-related reactions. The primary endpoint is dose-limiting toxicity (DLT). Secondary endpoints include pathological complete response (pCR), pathological downstaging, safety, and survival outcomes. Exploratory analyses will evaluate changes in immune cell populations in tumor tissues, lymph nodes, and peripheral blood.

The results of this study aim to provide evidence for new neoadjuvant strategies targeting lymph node metastatic bladder cancer and support the development of personalized therapeutic approaches.

Conditions

• Bladder Urothelial Carcinoma
• Lymph Node Metastasis

Interventions

DRUG

propranolol

Propranolol will be administered orally as a non-selective β-adrenergic receptor blocker. Treatment will start at a low dose and may be escalated to a maximum of 40 mg twice daily if tolerated. Vital signs will be monitored regularly, and dose adjustment, interruption, or discontinuation may occur based on predefined cardiovascular safety criteria.

DRUG

Tislelizumab

Tislelizumab will be administered intravenously as an anti-PD-1 monoclonal antibody according to standard dosing schedules for neoadjuvant immunotherapy. Infusion monitoring will be conducted in a facility equipped for emergency management. Dose interruption or discontinuation may occur if immune-related adverse events develop.

DRUG

gemcitabine

Gemcitabine will be administered intravenously as part of the gemcitabine/cisplatin chemotherapy regimen during neoadjuvant treatment. Hematologic parameters and organ function will be regularly monitored, and chemotherapy dose may be modified based on toxicity and tolerability according to institutional standards.

DRUG

Cisplatin

Cisplatin will be administered intravenously as part of the gemcitabine/cisplatin regimen. Renal function, electrolyte balance, and hematologic tests will be routinely monitored. Dosing may be adjusted or withheld according to predefined safety criteria and institutional guidelines for cisplatin-based chemotherapy.

Sponsors & Collaborators

• Peking University People's Hospital

  collaborator OTHER

• Fuzhou University Affiliated Provincial Hospital

  collaborator OTHER

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2028-12-31

Completion

2029-06-30

Countries

• China

Study Locations