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 10074879Term: Extrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; 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: PTClassification code 10017614Term: Gallbladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-003707-19-DE
• Lead Sponsor: Merck KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-13
• Last Update Posted: 4 April 2022

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 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 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.
5. Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1 and verified independently by 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.
8. 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.
9. 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.
10. Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) = 1.5 × ULN unless the participant is receiving anticoagulant therapy.
11. Albumin = 3.0 g/dL.
12. 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.
13. Adequate

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 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. 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.
6. 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.
7. 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.
8. History of non-infectious ILD requiring systemic steroid treatment, or current pneumonitis.
9. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before enrollment.
10. Known severe hypersensitivity (Grade = 3 NCI CTCAE 5.0) to investigational product or any components in their formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
11. Persisting Grade > 1 NCI CTCAE 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy Grade = 2 is acceptable.
12. 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 (= NYHA class II), or serious cardiac arrhythmia.
13. Clinically relevant diseases (e.g., inflammatory bowel disease) and/or uncontrolled medical conditions. Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for study intervention are also excluded.
14. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
15. Participa

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified