Last updated on November 2018

Durvalumab Plus Tremelimumab Combination Immunotherapy With or Without Weekly Paclitaxel in Patients With Advanced Biliary Tract Carcinoma (BTC) After Failure of Platinum-based Chemotherapy

Brief description of study

IMMUNO-BIL is a non-comparative randomized 1:1 phase II study. This study will assess the efficacy and safety of the combination of durvalumab plus tremelimumab with or without weekly paclitaxel in patients with advanced BTC after failure of platinum-based chemotherapy.

Detailed Study Description

Biliary tract carcinoma (BTC, adenocarcinoma in more than 90% of cases) is the second primary liver tumor in incidence after hepatocellular carcinoma (2,000 new cases/year in France).

The prognosis of biliary malignancies is poor, with a 5-year overall survival rate (OS) of about 10-15%, most often due to late diagnosis, at an advanced stage.

In advanced BTC, the gemcitabine plus platinum (cisplatin [GEMCIS] or oxaliplatin [GEMOX]) doublet of chemotherapy is the standard first-line treatment and no targeted therapy has been validated in this indication to date. There is no second-line therapeutic standard; chemotherapy (mainly, 5-FU-based combination) yields limited median progression-free survival (PFS) and OS of abouty 2-3 months and 6-7 months respectively, justifying the exploration of new therapeutic options.

Immune therapies (mainly, immune checkpoint inhibitors [ICI]) have opened new opportunities in cancer therapy. Hence, anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies (mAb) have demonstrated robust clinical activity and obtained FDA approval in several cancers. Recent data showed encouraging results with anti-PD-1 mAb as a monotherapy in PD-L1-positive pre-treated advanced BTC. The effects of ICI in combination with second-line chemotherapy in patients with advanced BTC have not been explored to date.

Platinum salts can induce "immunogenic cell death". Therefore, previous treatment with platinum may increase tumor immunogenicity and sensitivity to immune therapy, particularly, ICI. The second-line setting after failure of platinum-based chemotherapy may then be an optimal biological context for testing immune therapy in advanced BTC.

Durvalumab is a human immunoglobulin (Ig) G1 kappa (IgG1) anti-PD-L1 mAb. Tremelimumab is a human IgG2 anti-CTLA-4 mAb. Paclitaxel is a chemotherapy belonging to the taxane family. Taxanes may enhance the effect of immunotherapy by increasing the sensitivity of the tumor and activating the immune system. Taxanes are used in some patients with advanced biliary cancer.

These data suggest that BTC may be a good candidate for immune therapy. The combination of anti-CTL4 and anti-PD1/PD-L1 mAb is expected to be active in both immune-inflamed and non-inflamed BTC, and in PD-L1 high and low tumors.

Clinical Study Identifier: NCT03704480

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Institut Hospitalier franco-Britannique

Levallois-Perret, France
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Institut Curie

Saint Cloud, France
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Insitut Gustave Roussy

Villejuif, France
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CHI Poissy Saint Germain

Saint-Germain-en-Laye, France
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Recruitment Status: Open

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