Durvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)

A Phase IIIb, Single Arm, Open-label, Multicentre Study of Durvalumab in Combination With Chemotherapy for the First Line Treatment for Patients With Advanced Biliary Tract Cancers (TOURMALINE)

A study to assess the safety and efficacy of durvalumab in combination with gemcitabine-based chemotherapy regimens in participants with aBTC.

This study involves assessing the safety and efficacy of durvalumab in combination with different gemcitabine-based chemotherapy regimens as first line therapy for aBTC. The target population of interest in this study is participants with aBTC who are ≥ 18 years of age and above legal age per local regulations with WHO/ECOG PS of 0 to 2 at enrolment and who are not eligible for locoregional therapy. Participants with WHO/ECOG PS 2 will be capped at 20% of the overall treated participant population.

The study consists of 4 periods: screening period (Day-28 to Day -1), treatment period up to 8 cycles of gemcitabine-based chemotherapy regimens with durvalumab, maintenance treatment with durvalumab alone or in combination with gemcitabine-based chemotherapy (with the exception of paclitaxel), and then safety and survival follow-up.

Inclusion Criteria:

• Histologically confirmed, unresectable advanced or metastatic biliary tract carcinoma (BTC) including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma, and ampulla of Vater (AoV) carcinoma
• Participants with unresectable or metastatic BTC
• A World Health Organisation Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) of 0 to 2
• At least one lesion that qualifies as a Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) target lesion at baseline
• Adequate organ and bone marrow function
• Body weight of > 30 kg
• Negative pregnancy test (serum) for women of childbearing potential
• Female participants must be one year post-menopausal (amenorrhoeic for 12 months without an alternative medical cause)
• Male and female participants and their partners must be surgically sterile or on their chosen method of birth control as per the protocol.

Exclusion Criteria:

• Any evidence of diseases such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active interstitial lung disease/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations, history of uncontrolled or symptomatic cardiac disease, and history of allogenic organ transplant
• Active or prior documented autoimmune or inflammatory disorders
• History of another primary malignancy, except for malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study intervention
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Known to have tested positive for human immunodeficiency virus [HIV] (positive HIV 1/2 antibodies) or active tuberculosis infection
• Participants co-infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) or co-infected with HBV and Hepatitis D virus (HDV)
• Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 1) caused by previous anticancer therapy
• Central nervous system metastases requiring treatment or history of spinal cord compression
• Known allergy or hypersensitivity to any of the study intervention or any of the study intervention excipients.
• Any concurrent chemotherapy, other than the one allowed in the study, investigational medicinal product (IMP), biologic, or hormonal therapy for cancer treatment
• Palliative radiotherapy with a limited field of radiation within 2 weeks of the first dose of study intervention, or radiotherapy with a wide field of radiation or radiotherapy affecting more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention
• Major surgical procedure within 28 days prior to the first dose of IMP
• Prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines
• Receipt of the last dose of anticancer therapy within 28 days prior to the first dose of IMP