durvalumab with chemotherapy as first line treatment in patients with advanced biliary tract cancers (abtcs)

Conditions: Biliary Tract Cancer

Summary: 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.

Eligibility criteria:
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

Keywords: monoclonal antibodies pd-l1 antagonist durvalumab