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8110 Gatehouse Road, Falls Church, VA 22042

Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-TIM-3 Monoclonal Antibody BGB-A425 in Combination with Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients with Advanced Solid Tumors

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General Information

Age Group

Adults

Status

Recruiting

Protocol Number

NCT03744468

Background Information

This study will look at the safety and effectiveness of combining two investigational anticancer drugs, referred to as tislelizumab (also known as BGB-A317) and BGB-A425. Tislelizumab was recently approved in China for patients with relapsed or refractory classical Hodgkin’s lymphoma.

Tislelizumab and BGB-A425 are both monoclonal antibodies. An antibody is a common type of protein found in the body, through which the immune system finds and destroys bacteria, viruses, and other foreign molecules. Antibodies can also be produced in the laboratory and used for the treatment of patients. At present, several antibodies have been approved for the treatment of cancer and other diseases.

Tislelizumab targets PD-1, called programmed cell death-1, which is a protein present on the surface of immune cells. The PD-1 protein becomes active when its matched partner (called a ligand; PD-L1) binds to it like a handshake, and inhibits the body’s immune cells from killing tumor cells. The result of this binding is like stepping on a car brake. Tislelizumab can block PD-1 and PD-L1 (the ligand for PD-1) from binding to each other, thereby releasing the “brake” and restoring the tumor-killing function of immune cells. Similar to PD-1, the body’s immune cells have another protein present on their surface, which is referred to as TIM-3 or T-cell immunoglobulin and mucin-domain containing-3. The TIM-3 protein functions similar to PD-1 and works together with PD-1 to further stop the body’s immune cells from potentially killing tumor cells. Like PD-1, TIM-3 becomes active when it binds to one of its ligands. The BGB-A425 antibody works by blocking the interaction between TIM-3 and its ligands to further release the “brake” on the immune cells, which may increase the tumor-killing capacity of the immune cells.

This study aims to determine the safe dose range of BGB-A425 that can be used in combination with a single standard dose of tislelizumab, what the side effects are when taking these drugs together, how the body copes with these drugs and if these drugs shrink the tumors.

Offered At

Inova Schar Cancer Institute
8081 Innovation Park Drive
Fairfax, VA 22031
A department of Inova Fairfax Hospital

Eligibility Information

  • Adults over the ages of 18
  • Participant has not received prior therapy targeting TIM-3
  • Participants with one of the following histologically or cytologically confirmed solid tumors:
    • Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy)
    • Locally recurrent Stage IIIB or Stage IV squamous or non-squamous non-small cell lung cancer
    • Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology
  • Additional eligibility in protocol

Ineligibility Information

  • Pregnancy/breastfeeding
  • Participants with non-squamous NSCLC in Phase 2 Cohort 2, participants with known sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion are excluded. All participants with non-squamous histology must have been tested locally for EGFR, ALK, and ROS1 status. Use of an FDA-approved or local
  • Active leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with equivocal findings or with confirmed brain metastases are eligible for enrollment provided they are asymptomatic and radiologically stable without the need for CNS disease related corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)
  • Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy, with the following exceptions:
    • Controlled type I diabetes
    • Hypothyroidism (provided it is managed with hormone replacement therapy only)
    • Controlled celiac disease
    • Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
    • Any other disease that is not expected to recur in the absence of external triggering factors (requires consultation with the medical monitor prior to enrollment)
  • Any active malignancy ≤ 2 years before the first dose of study drug(s), except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
  • Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before administration of study drug
  • History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases, including pulmonary fibrosis, acute lung diseases, etc.
  • Uncontrolled diabetes, > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drug
  • Infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug(s), or a requirement for chronic prophylactic treatment with antibiotics
    • Note: antiviral therapy is permitted for eligible patients with HBV infection
  • A known history of HIV infection • Participants with untreated chronic hepatitis B or chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (or 2500 copies/mL) or patients with detectable HCV RNA at screening
  • Diagnosis of prior immunodeficiency or has undergone prior allogeneic stem cell transplantation or organ transplantation
  • History of cardiovascular illnesses
  • Additional ineligibility in protocol

Additional information can be found at: https://clinicaltrials.gov/ct2/show/NCT04457596