Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer

Shanghai Jiao Tong University

Status and phase: Unknown; Phase 2

Conditions: Muscle-Invasive Bladder Carcinoma

Treatments: Drug: Cisplatin; Drug: Tislelizumab; Drug: Gemcitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT04909775

RJBS-001

Details and patient eligibility

About

This study is designed prospectively to investigate the safety, efficacy and feasibility of cisplatin-based chemotherapy combined with tislelizumab as bladder sparing treatment for patients with muscle invasive bladder cancer (MIBC) which are eligible for cisplatin. The patients that achieved clinical remission after 4 cycles of cisplatin/gemcitabine and tislelizumab, will receive tislelizumab maintenance therapy for a year or 13 cycles. Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071).

This trial investigates the efficacy of cisplatin-based chemotherapy combined with Tislelizumab to induce clinical complete remission of muscle invasive bladder cancer and the feasibility to provide bladder sparing treatment for these patients.

Full description

The patients that meet the Inclusion and Exclusion Criteria will treat with 4 cycles of cisplatin-based chemotherapy combined with Tislelizumab (200mg per cycle) prior to cystectomy discussion. The patients that show clinical benefit will receive tislelizumab for bladder sparing. Forty patients will be enrolled in this trial.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 18 and ≤75 years old on day of signing informed consent
• Signing informed consent
• Patients with histologically confirmed muscle-invasive bladder cancer (cT2-T4, N0, M0) and with strong intent to bladder sparing(Patients with mixed histology, predominantly transitional cells, could be enrolled. )
• Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 15 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.
• ECOG performance status of 0 or 1
• Adequate organ and marrow function for cisplatin treatment
• No received prior therapy with systemic chemotherapy or immunotherapy

Exclusion criteria

• Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any approved anticancer therapy within 28 days before enrollment
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis
• Participants with uncontrolled hypercalcemia
• Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
• History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases
• A known history of HIV infection
• Prior allogeneic stem cell transplantation or organ transplantation
• History of severe hypersensitivity reactions to other monoclonal antibodies
• History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Arm 1

Experimental group

Description:

Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.

Treatment:

Drug: Gemcitabine

Drug: Cisplatin

Drug: Tislelizumab