Safety and Efficacy Study of Tislelizumab in Combination With BCG in HR-NMIBC Patients (TACBIN-01)

Trial end date:
Target enrollment:
Participant gender:
This study is a single-arm, open-label, single-center study to assess the safety of tislelizumab with BCG, and to obtain the preliminary efficacy results in subjects who have been diagnosed with high-risk NMIBC without prior BCG treatment.
Phase 1/Phase 2
Accepts Healthy Volunteers?
Lead Sponsor:
RenJi Hospital
Huidu Shanghai Medical Sciences Ltd
Inclusion Criteria:

- Adult man and women, 18-75 years old ECOG PS 0-1

- Life expectancy ≥1year

- Any high risk non muscle invasive urothelial carcinoma histologically confirmed
defined on the TURBT within 6weeks as any of the following :

- T1 tumor and/or

- High grade (WHO 2004) and/or Grade 3 (WHO1973) and/or

- Carcinoma in situ (CIS)

- Underwent TURBT to remove all resectable disease (residual CIS acceptable) within 6
weeks before recruitment and confirm absence of muscle invasion. The restagingTURBT is
acceptable, but the interval between the two TURBTs is 2-6 weeks;

- Absence of metastasis in pelvis, abdomen, or chest, as confirmed by a negative
baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan no more
than 3m prior to the first study treatment

- BCG-naïve defined as:

- Chemotherapy failure but BCG naïve: patients who have received at least six of eight
induction doses of chemotherapy(including immediate single instillation)have a high
risk of recurrence within 1 year; but have not received BCG perfusion in the bladder;

- Treatment-naïve: patients who have not received prior intravesical chemotherapy or
BCG, but who previously received but stopped chemotherapy or BCG more than 3 years
before study entry are eligible

- Adequate hematologic and organ function, as defined by the following laboratory
results obtained within 14 days prior to the first dose:

- white blood cell (WBC) counts ≥ 3.0× 109/L

- absolute neutrophil count (ANC) ≥1.5 ×109/L

- Platelet count ≥ 75 ×109/L

- Hemoglobin ≥ 9.0 g/dL

- Serum albumin ≥ 30g/L

- aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase(ALP) ≤2.5 × the upper limit of normal (ULN)

- Serum bilirubin ≤1.0 × ULN

- Partial thromboplastin time (PTT)/Prothrombin Time (PT) ≤1.5 × ULN or international
normalized ratio (INR) <1.7 × ULN

- Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)

- Female participants of childbearing potential have a negative urine or serum pregnancy
test before recruitment. Female or male must be willing to use an adequate method of
contraception during the treatment period and for at least 5 months after the last
dose of tislelizumab

- Patient is willing and able to sign a written informed consent document and comply
with the protocol for the duration of the trial including undergoing treatment and
scheduled visits, and examinations including follow-up.

Exclusion Criteria:

- Muscle-invasive, locally advanced non-resectable, or lymph node positive, or
metastatic urothelial carcinoma; previous or accompanied by upper urinary tract
urothelial carcinoma (UTUC)

- There are pathological variants or non-urothelial cancer components in the very high
risk of NMIBC

- T1 high-grade (HG/G3) combined with urothelial carcinoma of the prostate urethra

- Pathological tissue specimens with lymphovascular infiltration or special type of
urothelial carcinoma after TURBT*

*Special types of urothelial carcinoma: adenoid differentiation, squamous
differentiation, neuroendocrine differentiation, plasma cell-like changes and
micropapillary changes, etc.

- Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including
anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

- The diagnosis of HR NMIBC was followed by induction intravesical chemotherapy, but
immediate single instillation (within 24 hours after surgery) was allowed before the
pathological results were not clear. The drugs include mitomycin, pirarubicin,
doxorubicin, epirubicin, CHPT or gemcitabine;

- Treatment with anti-cancer therapy including systemic immunostimulatory agents
(including but not limited to INF, IL-2any), chemotherapy, radiation therapy, or
hormonal therapy or any other investigational agent.

- Any unresolved toxicity (CTCAE grade 2 or above) from previous anti-cancer therapy.

- Active autoimmune disease that has required systemic treatment in the past 2 years,
including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease and so on.

- Patients with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days before first dose. The use of inhaled or low-dose (e.g., ≤10 mg/day prednisone)
corticosteroids is allowed.

- Known HIV, active Hepatitis B or C infection or tuberculosis.

- Infections ≥ 3 grade within 4 weeks, including but not limited to severe urinary tract
infection, severe pneumonia, infectious complications, bacteremia intravenous
antibiotic therapy or hospitalization patients receiving therapeutic oral or IV
antibiotics within 1 weeks prior to the first dose are not eligible.

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.

- Allergy or hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary
cells or any component of the tislelizumab or BCG formulation

- Prior allogeneic stem cell or solid organ transplant

- Major surgical procedure other than for diagnosis within 4 weeks prior to the first
dose or anticipation of need for a major surgical procedure during the study

- Patients who have any of the following cardiac conditions:

- Poorly controlled diabetes (after treatment with glycosylated hemoglobin [HbA1c]> 8%);

- Poorly controlled High blood pressure evaluated by the investigator (blood pressure

- Cardiac insufficiency (including left ventricular ejection fraction [LVEF] <50%),
myocardial infarction within the past 6 months, arrhythmia or unstable angina that
cannot be well controlled by medication.

- Pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease
or clinically significant lung function test abnormalities; oother conditions that the
treating physicians believe may endanger the health of the patients by their
participation in this clinical trial.

- Administration of a live, attenuated vaccine within 4 weeks prior to first dose,
during treatment or within 8 weeks following the last dose of tislelizumab Note:
Seasonal vaccines for influenza are generally inactivated vaccines and are allowed.

- Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer, in situ
cervical cancer, prostate cancer without evidence of PSA progression or carcinoma in
situ such as the following: gastric, prostate, cervix, colon, melanoma, or breast for

- Have a mental illness, restricted or incapable of civil conduct, and a known history
of psychotropic drug abuse. It may increase the risk of participating in the research,
or interfere with the results of the research, and patients who the researcher
believes are not suitable for participating in this research.