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

NCT04922047 | Unknown Phase 1 DMC

• 2 other identifiers: KY2021-041BGB-A317-2002-IIT
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Antineoplastic Agents; Urinary Bladder Diseases; Tislelizumab Antineoplastic Agents, Immunological

Keywords

bladder carcinoma; BCG; PD-1

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT)

  Safety

  28 days of single infusion

Secondary Outcomes (3)

• Event Free Survival (EFS) rate at 24 months

  approximately 24 months

• Progression free survival (PFS) rate at 36 months

  approximately 36 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  approximately 24 months

Other Outcomes (1)

• Biomarker (Tissue, liquid biopsy)

  approximately 24 months

Study Arms (1)

Experimental: Intravenous tislelizumab / Intravesical BCG

EXPERIMENTAL

Drug: tislelizumab / BCG Tislelizumab 200 mg administered by intravenous infusion every 3 weeks in first year and continue to second year based on physician choose. BCG 120 mg induction therapy administered via intravesical instillation (once weekly for 6 weeks). BCG induction therapy is followed by maintenance therapy (once weekly for 3 weeks at months 3, 6, 12, 18, 24m). Other Name: BGB-A317

Drug: tislelizumab and BCG

Interventions

tislelizumab and BCG DRUG

Tislelizumab 200 mg administered by intravenous infusion every 3 weeks in first year and continue to second year based on physician choose. BCG 120 mg induction therapy administered via intravesical instillation (once weekly for 6 weeks). BCG induction therapy is followed by maintenance therapy (once weekly for 3 weeks at months 3, 6, 12, 18, 24m).

Experimental: Intravenous tislelizumab / Intravesical BCG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RenJi Hospital: lead
• BeiGene: collaborator
• Huidu Shanghai Medical Sciences Ltd: collaborator

Study Sites (1)

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

Related Links

• Investigator Link

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Urinary Bladder Diseases

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Wei XUE, MD, PHD

  Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruiyun Zhang, MD, MSc

CONTACT

008613681687457; zhangruiyun4337@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2021
• First Posted: June 10, 2021
• Study Start: June 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: August 1, 2023
• Last Updated: June 11, 2021

Record last verified: 2021-06

Locations

CN (1)