Phase II Study of M7824 Monotherapy in Participants With Locally Advanced or Metastatic Biliary Tract Cancer Who Fail or are Intolerant to First-line Platinum Based Chemotherapy

Phase 1

Conditions: Biliary Tract Cancer
MedDRA version: 20.0Level: LLTClassification code 10028982Term: Neoplasm biliary tractSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10074879Term: Extrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10017614Term: Gallbladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003707-19-FR

Lead Sponsor: Merck KGaA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 141

Inclusion Criteria

1. 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.
2. Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC.
3. Availability of tumor (primary or metastatic) archival material or fresh biopsies (collected within 28 days before first administration of study intervention) 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.
4. Participants with BTC must have failed or be intolerant to 1L systemic platinum-based chemotherapy. 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.
5. Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1 and verified independently by an Independent Review Committee (IRC).
6. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at study entry and Day 1 of treatment with M7824.
7. Life expectancy = 12 weeks as judged by the Investigator.
9. Adequate hematological function defined by white blood cell (WBC) count = 3 × 109/L with absolute neutrophil count (ANC) = 1.5 × 109/L, lymphocyte count = 0.5 × 109/L, platelet count = 75 × 109/L, and hemoglobin (Hgb) = 9 g/dL (in absence of blood transfusion).
10. 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.
11. Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) = 1.5 × ULN unless the participant is receiving anticoagulant therapy.
12. Albumin = 3.0 g/dL.
13. 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.
14. 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 + Crenzume.
15. Male participants are eligible to participate if they agree to the appr

Exclusion Criteria

1. Ampullary cancer is excluded.
2. Rapid clinical deterioration other than malignancy which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or study procedures.
3. 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.
5. 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 HIV or known acquired immunodeficiency syndrome.
• Active tuberculosis infection (clinical symptoms, physical or radiographic, and laboratory findings)
• Active bacterial or fungal infection requiring IV systemic therapy (except as indicated, discuss alternative scenarios with the Medical Monitor).
6. 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 is acceptable.
8. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before enrollment.
9. Known severe hypersensitivity (Grade = 3 National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 [NCI CTCAE 5.0]) to investigational product (M7824) or any components in their formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
10. Persisting Grade > 1 NCI CTCAE 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy Grade = 2 is acceptable.
11. 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.
12. 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.
13. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
14. Participants who are not eligible for or have not been treated with 1L systemic chemotherapy will be excluded.
15. Concurrent treatment with nonpermitted drugs.
16. Prior participation in a M7824 clinical trial.
17. Prior therapy with other immunotherapy or checkpoint inhibitors, such as anti-PD 1, anti PD L1, anti- cytotoxic T-cell lymphocyte-4 (CTLA-4) antibodies.
18. Prior therapy with any antibody or inhibitors targeting the

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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