Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients (BladderGATE) (BladderGATE)

  • End date
    Feb 21, 2024
  • participants needed
  • sponsor
    Fundacion Oncosur
Updated on 21 March 2022
tumor cells
carcinoma in situ
bladder cancer
bacillus calmette-guerin
transurethral resection
carcinoma of the bladder
expression by immunohistochemistry


Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are usually managed by transurethral resection of their bladder tumor (TURBT) alone plus additional intravesical therapy to deliver high local concentrations of a therapeutic agent within the bladder, potentially destroying viable tumor cells that remain following TURBT. Although the exact mechanism of bacillus Calmette-Guerin (BCG) antitumor action is unknown, its intravesical instillation triggers a variety of local immune responses, which appear to correlate with antitumor activity. BCG induction plus maintenance is the current, guideline-recommended standard of care for high-risk NMIBC. Both recent evidence and guidelines suggest that full-dose BCG maintenance after the first BCG dose of induction course as used in the SWOG 8507 and European Organization for Research and Treatment of Cancer (EORTC) 30911 and 30962 trials, is the most appropriate maintenance schedule. High-risk NMIBC patients following adequate treatment have a recurrence rate at 1 and 2 years of 25 and 30% respectively after treatment with the current standard (BCG), which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. It is implicated in tumor immune escape by inducing apoptosis of activated antigen-specific CD8 T-cells, impairing cytokine production and diminishing the toxicity of activated T-cells. PD-L1 expression by immunohistochemistry using the Ventana SP142 assay on tumor-infiltrating immune cell (IC) status defined by the percentage of PD-L1 positive ICs: IC0 (<1%); IC1 (≥1% but<5%); and IC2/3 (≥5%PD-L1) has been demonstrated to be higher (IC2/3) in resection and TURBT specimens versus biopsies from primary lesions or metastatic sites. In patients with metastatic bladder cancer, treatment with the PD-L1 inhibitor atezolizumab (1200 mg, every 3 weeks) resulted in objective response rates of 26% in the IC2/3 group, 18% in the IC1/2/3 group and 15% in all patients. The median overall survival was 11.4 months in the IC2/3 group, 8.8 months in the IC1/2/3, and 7.9 months in all patients. Grade 3-4 related treatment-related adverse events occurred in 16% and grade 3-4 immune-mediated adverse events occurred in 5% of treated patients. In murine models with invasive bladder cancer, anti-PD-1 plus CpG has shown to increase survival in mice, with anti-PD-1 plus CpG being superior to either agent alone. Taken together, these results confirmed the clinical activity of atezolizumab in metastatic bladder cancer, which could be beneficial in patients with NMIBC in combination with standard approaches such as BCG.

Condition Invasive Bladder Cancer
Treatment Atezolizumab, BCG
Clinical Study IdentifierNCT04134000
SponsorFundacion Oncosur
Last Modified on21 March 2022


Yes No Not Sure

Inclusion Criteria

Patients ≥ 18 years old
Signed Informed Consent Form
Histologically confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta
G3- and / or carcinoma in situ) transitional cell carcinoma of the bladder
Never treated with BCG or stopped >3y ago
World Health Organization Performance Status (WHO PS) 0-1
No prior radiation to bladder
Life expectancy ≥ 5 years
Adequate hematologic and end-organ function
The time elapsed between the TURBT and the start of the study treatment will not be less than 4 weeks or more than 12 weeks
Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 14 days prior to the first dose of study treatment
For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 150 days after the last dose of study drug
Tumor tissue biopsy at study entry or availability of an archival specimen obtained within 2 months of study screening
Willingness to complete all study-related procedures including patient-reported questionnaires

Exclusion Criteria

Muscle-invasive, locally advanced non-resectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or stage IV)
Previous BCG within a 3 years period
Life expectancy <5 years
WHO PS 2, 3 or 4
Known additional malignancy that is progressing or requires active treatment
Active autoimmune disease that has required systemic treatment in the past 2 years
Evidence of interstitial lung disease or active non-infectious pneumonitis
Active infection requiring systemic therapy
Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 150 days after the last dose of study treatment
Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
Known human immunodeficiency virus (HIV)
Known active Hepatitis B or C infection or tuberculosis
Received a live virus vaccine within 30 days of planned start of study treatment
Treatment with any approved anti-cancer therapy, including chemotherapy , radiation therapy , or hormonal therapy within 3 weeks prior to the first dose of study treatment
Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to the first dose of study treatment
Allergy or hypersensitivity to components of the atezolizumab or BCG formulation
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
Serum albumin < 2.5 g/dL
Severe infections within 4 weeks prior to the first dose of study treatment
Signs or symptoms of infection within 2 weeks prior to the first dose of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
Major surgical procedure other than for diagnosis within 4 weeks prior to the first dose of study treatment, or anticipation of need for a major surgical procedure during the course of the study
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
History of prior systemic BCG infection
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