Gemcitabine, Cisplatin, Nab-paclitaxel (GAP) and Cemiplimab for Locally Advanced Biliary Tract Cancer (BTC)

Inclusion Criteria: * Histologically confirmed diagnosis of biliary tract adenocarcinoma (intra- or extra-hepatic, and gallbladder) * Locally advanced, unresectable BTC without evidence of distant metastatic disease. Patients with surgically unresectable BTC on diagnostic abdominal CT scan or MRI are eligible to participate in the study. Unresectable, locally advanced, but non-metastatic BTC must be confirmed with the designated site radiologist and surgeon at the treating institution (Appendix 2) and must meet at least one of the following criteria: * Tumor involvement of both hepatic lobes and/or vessels * Vascular invasion of the portal vein or main hepatic artery * For perihilar tumors: bilateral hepatic duct involvement up to secondary radicles * Atrophy of one liver lobe with invasion of contralateral vessel and/or bile duct * Extrahepatic organ tumor invasion, except contiguous involvement of the diaphragm * Inadequate estimated liver remnant after surgery If resectability cannot be determined based on CT or MRI, an FDG-PET may be performed, and if it cannot be determined based on imaging alone, surgical exploration is permitted. * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of cemiplimab added to gemcitabine, cisplatin, and nab-paclitaxel in participants \<18 years of age, children are excluded from this study. * Treatment naïve; no prior systemic therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy of greater than 3 months. * Have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 13.3 for more information regarding evaluation of measurable disease. * Adequate hematological and organ function (test results from within 14 days prior to initiation of study treatment): * Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L without granulocyte colony-stimulating factor support * White blood cell (WBC) count ≥ 2.5 x 10\^9/L (2500/uL) * Lymphocyte count ≥ 0.5 x 10\^9/L (500/uL) * Platelet count ≥ 100 x 10\^9/L (100,000/uL) without transfusion * Hgb ≥ 9.0 g/dL * AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) * Total bilirubin ≤ 1.5 × ULN, unless in patients with known Gilbert disease (≤ 3 × ULN), or unless elevated secondary to biliary obstruction due to malignancy amenable to decompression prior to administration of investigational therapy * Creatinine within ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min using the Cockcroft-Gault formula * International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN, except for those on stable anticoagulation for at least two weeks * Liver function Child-Pugh class A or B7, if there is evidence of cirrhosis * Criteria for known hepatitis B and C positive subjects: * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment. Participants should remain on antiviral therapy throughout the study and follow local guidelines for HBV anti-viral therapy after the completion of the study. * Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative antiviral therapy at least 4 weeks prior to enrollment. * Subjects who are HIV positive are eligible if their viral load is undetectable at screening and their CD4+ T cell count is ≥ 200 cells/mm3. Caution should be exercised for subjects on antiretrovirals that may be inhibitors or inducers of CYP2C8 or CYP3A4. * Negative pregnancy test: Women of child-bearing potential must have a negative serum pregnancy test at screening and must agree to use an effective form of contraception from the time of the negative pregnancy test until a minimum of 3 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive (injectable or implantable) in conjunction with a barrier method. Women of non-child-bearing potential must have been postmenopausal for ≥ 1 year or surgically sterile. * Birth control agreement: The effects of cemiplimab on the developing human fetus are unknown. For this reason and because immunotherapy agents and cytotoxic chemotherapy used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of treatment. * The participant must understand and be willing to sign a written informed consent document which includes agreement that the participant (or insurance) will be charged gemcitabine, cisplatin, nab-paclitaxel. * The participants must be able to comply with the study protocol, according to the investigator's judgment. Exclusion Criteria: * Histologies other than adenocarcinoma such as mixed hepatocellular carcinoma/cholangiocarcinoma, adenosquamous carcinoma or mixed adenocarcinoma/neuroendocrine carcinoma; ampullary carcinomas are also excluded. * Has initially resectable disease or distant metastasis, including distant lymph nodes. Resectable BTC include the following: absence of retropancreatic and paraceliac nodal metastases or distant liver metastases, absence of invasion of the portal vein or main hepatic artery, absence of extrahepatic adjacent organ invasion, absence of disseminated disease. * Participants may not have had systemic chemotherapy, investigational therapy, or treatment with T-cell co-stimulating or immune check point blockade therapies (including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic antibodies) prior to initiation of study treatment. * Participants receiving any other investigational agents concurrently or other anti-neoplastic agents (hormone therapy acceptable) * Participants may not have had previous radiotherapy for the biliary tract tumor. * Patients may not have had surgical resection of biliary tract cancer prior to initiation of study intervention. * Participants may not have undergone major surgery or experienced significant traumatic injury within 14 days prior to initiating study treatment or be recovering from procedure-related adverse events of \> Grade 1. * An active autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: * 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 and is allowed. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met: * Rash must cover \< 10% of body surface area; * Disease is well-controlled at baseline and requires only low-potency topical corticosteroids; * No occurrence acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months. * History of (non-infectious) idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan (history of radiation pneumonitis or fibrosis in the radiation field is permitted). * History of allergic reactions attributed to compounds of similar chemical or biologic composition to cemiplimab, gemcitabine, cisplatin, or nab-paclitaxel; or known allergy or sensitivity to any of the study drug excipients. * History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins. * Peripheral neuropathy \> Grade 2. * A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, calcineurin inhibitors, and anti-tumor necrosis factor alpha agents) within two weeks prior to initiation of study treatment, or anticipate the need for systemic immunosuppressive medication during the course of the study, except for a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after approval from the Principal Investigator. * A known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ), excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. * An active infection requiring systemic therapy. * Active tuberculosis * Concurrent active hepatitis B defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C (defined as anti-HCV Ab positive and detectable HCV RNA) infection. * Received colony-stimulating factors (e.g., granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention. * Significant cardiovascular disease: Patient may not have significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 12 months prior to initiation of study treatment, seizure disorder, uncontrolled hypertension, or unstable arrhythmia or unstable angina within 3 months prior to initiation of study treatment. * Baseline QTcF ≥ 450 ms (males) or ≥ 470 ms (females) * History of autologous stem cell, allogenic stem cell, or solid organ transplant. * Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipate the need for such a vaccine during treatment with cemiplimab or within 5 months after the last dose of cemiplimab. * History or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating clinician. * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because cemiplimab, gemcitabine, cisplatin, and nab-paclitaxel have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated with cemiplimab, gemcitabine, cisplatin, and nab-paclitaxel. * In the judgment of the Investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.