Inclusion Criteria: 

• Are ≥ 18 years of age at the time of signing the informed consent. In Japan, if a participant is at least 18 but < 20 years of age, written informed consent from his/her parent or guardian will be required in addition to the participant’s written consent.
• Are participants with histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer (BTC). 
• Availability of tumor (primary or metastatic) archival material or fresh biopsies is mandatory. Fine needle aspirates, transductal aspirates, or cell blocks are not acceptable.  Endoscopic retrograde cholangiography or intraductal ultrasounds assisted biopsy is acceptable, needle or excisional biopsies, or resected tissue, are preferable. Tumor biopsies and tumor archival material must be suitable for biomarker assessment as described in the Laboratory Manual.
• Participants with BTC must have failed or be intolerant to 1L systemic platinum-based chemotherapy administered for locally advanced or metastatic disease. Only one prior treatment line is allowed. Participants who received adjuvant platinum-based chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible. If recurrence occurs during or within 6 months after the adjuvant chemotherapy, adjuvant platinum-based chemotherapy is counted as 1L chemotherapy.
• Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1 and verified independently by IRC..
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1 at study entry and Day 1 of treatment with M7824.
• Life expectancy ≥ 12 weeks as judged by the Investigator.
• Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 10^9/L with absolute neutrophil count ≥ 1.5 × 10^9/L, lymphocyte count ≥ 0.5 × 10^9/L, platelet count ≥ 75 × 10^9/L, and hemoglobin (Hgb) ≥ 9 g/dL.
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × upper limit of normal (ULN), an aspartate aminotransferase (AST) level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN. For participants with liver  involvement in their tumor, AST ≤ 5.0 × ULN and ALT ≤ 5.0 × ULN is acceptable:
  • Participants with biliary obstruction should have an adequate biliary drainage with no evidence of ongoing infection. Biliary duct obstruction should be relieved by internal endoscopic drainage/stenting at least 2 weeks prior to  dosing or by palliative bypass surgery or percutaneous drainage prior to study entry, and the participant should have no active or suspected infection. Participants fitted with a biliary stent should be clinically stable and free of signs of infection for ≥ 2 weeks prior to dosing;
  • Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy.
• Albumin ≥ 3.0 g/dL.
• Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals (e.g., entecavir, tenofovir, or lamivudine; adefovir or interferon are not allowed) at study entry and with planned monitoring and management including baseline HBV DNA quantity according to appropriate labeling guidance.  Participants receiving active hepatitis C virus (HCV) therapy must be on a stable dose at study entry and with planned monitoring and management according to appropriate labeling guidance of an approved antiviral.
• Adequate renal function defined by either creatinine ≤1.5 × ULN or an estimated creatinine clearance (CCr) > 40 mL/min according to the Cockcroft-Gault formula or by measure of CCr from 24-hour urine collection.
  • CCr (mL/min) = (140-age) × weight (kg)/(72 × serum Cr jaffe);
  • If female, × 0.85;
  • If Cr is measured by enzymatic method, add 0.2 and use as Crjaffe = 0.2 + Crenzyme.
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 4 months after the last dose of study intervention:
  • Refrain from donating sperm PLUS; either
  • Abstain from intercourse with a female; OR
  • Use a male condom:
    • When having sexual intercourse with a woman of childbearing potential (WOCBP), who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of < 1% per year, as described in Appendix 3, since a condom may break or leak;
    • When engaging in any activity that allows for exposure to ejaculate.
• A female is eligible if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Not a WOCBP; OR
  • If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of < 1% per year), preferably with low user dependency, as described in Appendix 3 for the following time periods:
    • Before the first dose of the study intervention(s), if using hormonal contraception:
      • Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses; OR
      • Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay.
    • During the intervention period
    • After the study intervention period (i.e., after the last dose of study intervention is administered) for at least 2 months after the last dose of study intervention.
    • The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
  • Have a negative serum or highly sensitive urine pregnancy test, as required by local regulations, within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required.
• Additional requirements for pregnancy testing during and after study intervention are in Safety Assessments and Procedures.
• The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy.
• Can give signed informed consent, as indicated in Study Governance, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.

Exclusion Criteria:

• Ampullary cancer is excluded.
• Rapid clinical deterioration other than malignancy which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or study procedures.
• Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
• Other previous and/or intercurrent malignancy except for curatively treated cancers with no recurrence in > 3 years since treatment completion, or early cancers treated with curative intent, including cervical carcinoma in situ, superficial, noninvasive bladder cancer, or basal cell or squamous cell carcinoma in situ. Endoscopically resected early gastrointestinal cancers limited in mucosal layer (esophageal, gastric, and colorectal) that are without recurrence in > 1 year are allowed.
• Significant acute or chronic infections, including:
  • Uncontrolled biliary infection. Biliary tract obstruction should be released by stenting or percutaneous transhepatic biliary drainage;
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (no testing at Screening required). If an Investigator has a strong suspicion of HIV infection without known history for a participant in Screening, and the participant refuses testing, discuss with the Medical Monitor to assess eligibility.
    • Note: HIV testing is not mandated for study inclusion; however, if it is performed at any point in Screening or while on study, a site must consent the participant for HIV testing as per local standard guidance).
  • Active tuberculosis infection (clinical symptoms, physical or radiographic, and laboratory findings;
  • Active bacterial or fungal infection requiring intravenous systemic therapy (except as indicated, discuss alternative scenarios with the Medical Monitor).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
  • Participants with diabetes type 1, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;
  • Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg of prednisone or equivalent per day;
  • Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
• History of non-infectious (e.g., drug-induced) ILD requiring systemic steroid treatment, or current pneumonitis.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before enrollment.
• Known severe hypersensitivity (Grade ≥ 3 National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE v5.0]) to investigational product (M7824) or any components in their formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
• Persisting Grade > 1 NCI-CTCAE v5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy Grade ≤ 2 is acceptable.
• Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia.
• Clinically relevant diseases (e.g., inflammatory bowel disease) and/or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the participant’s tolerance or ability to participate in the study. Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for study intervention are also excluded.
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Participants who are not eligible for or have not been treated with 1L systemic chemotherapy will be excluded.
• Systemic anticancer treatment after failing 1L platinum-based chemotherapy.
• Concurrent treatment with nonpermitted drugs.
• Prior participation in a M7824 clinical trial.
• Prior therapy with other immunotherapy or checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies.
• Prior therapy with any antibody or inhibitors targeting the TGF-β/TGF-β receptor pathway.
• Anticancer treatment within 21 days before the start of study intervention; e.g., cytoreductive therapy, radiotherapy involving > 30% of the bone marrow (with the exception of palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
• Anticancer treatment with antibody within 28 days before the start of study intervention. 
• Systemic therapy with immunosuppressive agents within 7 days before the start of study intervention; or use of any investigational drug within 28 days before the start of study intervention.
• Vaccine administration within 4 weeks of M7824 administration. Vaccination with live vaccines while on study is prohibited. Administration of inactivated vaccines is allowed (e.g., inactivated influenza vaccines).
• Participation in experimental clinical studies after failure of 1L systemic chemotherapy.
• Unable to tolerate CT or magnetic resonance imaging (MRI) in the opinion of the Investigator and/or allergy to contrast material.
• Major surgery within 28 days before the start of study intervention (excluding prior diagnostic biopsy and stenting/percutaneous transhepatic biliary drainage for releasing biliary tract obstruction).
• Pregnancy or breast feeding.
• Known active or recent alcohol or drug abuse within 2 years.
• Legal incapacity or limited legal capacity.
• Other severe acute or chronic medical conditions.