Gemcitabine, Cisplatin, Quemliclustat and Zimberelimab for the Treatment of Patients with Advanced, Recurrent or Metastatic Biliary Tract Cancer

Inclusion Criteria

• Patients with cytologically or histologically confirmed BTC by American Joint Committee on Cancer (AJCC) version 8
• Patients must have late stage (locally advanced, recurrent or metastatic) BTC. Patients must not have received systemic treatment for advanced disease. Prior adjuvant therapy is allowed as long as recurrences occurred 6 months or later from all treatment completion
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Age ≥ 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days prior to registration
• Presence of measurable or evaluable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Platelet count ≥ 100,000 x 10^9/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Calculated creatinine clearance < 1.5 x upper limit of normal (ULN) OR 60 mL/min using the Cockcroft-Gault formula
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Patients with Gilbert’s syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Females of childbearing potential who are sexually active with a male able to father a child must have a negative pregnancy test (serum or urine) within 14 days prior to registration
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for up to 120 days after the last dose of study drug(s). Males able to father a child must be willing to abstain from heterosexual vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for up to 120 days after the last dose of study drug(s)
• Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee

Exclusion Criteria

• Prior therapy with gemcitabine, cisplatin, or any immune checkpoint inhibitors for the treatment of BTC
• Known hypersensitivity to recombinant proteins, or any excipient contained in treatment medication formulations
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study
• History of solid organ or allogeneic bone marrow transplantation
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study
• History of positive test results for hepatitis B surface antigen and/or hepatitis C virus antibody with presence of hepatitis C qualitative ribonucleic acid (RNA). Testing for viral hepatitis is not required during screening
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial
• Untreated central nervous system (CNS) metastasis. Screening of asymptomatic patients for CNS metastasis is not required for enrollment
• Underlying medical conditions that, in the investigator’s or sponsor’s opinion, will make the administration of investigational products (IP)(s) hazardous, including but not limited to * Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. * Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of the study treatments
• History of trauma or major surgery within 28 days prior to the first dose of IP. (Note that placement of central venous access catheter [e.g., port or similar] is not considered a major surgical procedure)
• Treatment with palliative radiation therapy within 14 days of study treatment initiation
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Significant dementia or other mental condition that precludes the participant’s ability to consent to the study
• Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational products