Study of Durvalumab Versus Placebo in Combination With Definitive Chemoradiation Therapy in Patient With ESCC

Study Overview
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Brief Summary
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This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study to assess the efficacy and safety of durvalumab administered concurrently with dCRT in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC).

Detailed Description
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Approximately 600 patients with locally advanced, unresectable ESCC (AJCC 8th cStage II-IVA) will be randomized in a 2:1 ratio to receive either durvalumab + dCRT or placebo + dCRT. The primary objectives of this study are to assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of progression free survival (PFS, per RECIST 1.1 as assessed by BICR) in PD-L1 High population.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo Controlled, Multi-Center, International Study of Durvalumab Given Concurrently With Definitive Chemoradiation Therapy in Patients With Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma (KUNLUN)

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Placebo
* Drug: cisplatin + fluorouracil
* Drug: cisplatin + capecitabine
* Radiation: Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older at the time of signing the ICF. Histologically or cytologically confirmed esophageal squamous cell carcinoma, and present with locally advanced disease (Stage II-IVA). Unresectable or refusing surgery, and has been deemed suitable for definitive chemoradiation therapy. Patients with at least an evaluable lesion per RECIST 1.1. Mandatory provision of available tumor tissue for PD-L1 expression analysis. ECOG PS 0 or 1. Adequate organ and marrow function. Life expectancy of more than 3 months. Exclusion Criteria: Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma. Prior anti-cancer treatment for ESCC. Patient with a great risk of perforation and massive bleeding. History of allogeneic organ transplantation. Active or prior documented autoimmune or inflammatory disorders. Uncontrolled intercurrent illness. History of another primary malignancy. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Durvalumab + definitive CRT<br>Durvalumab + concurrent chemoradiation | Drug: Durvalumab<br>* Durvalumab intravenous infusion<br>* Other names: MEDI4736;Drug: cisplatin + fluorouracil<br>* cisplatin + fluorouracil, as per Standard of Care<br>Drug: cisplatin + capecitabine<br>* cisplatin + capecitabine, as per Standard of Care<br>Radiation: Radiation<br>* 50-64Gy in total<br>|
| Placebo Comparator: Arm 2: Placebo + definitive CRT<br>Placebo + concurrent chemoradiation | Drug: Placebo<br>* Durvalumab matching placebo for intravenous infusion<br>Drug: cisplatin + fluorouracil<br>* cisplatin + fluorouracil, as per Standard of Care<br>Drug: cisplatin + capecitabine<br>* cisplatin + capecitabine, as per Standard of Care<br>Radiation: Radiation<br>* 50-64Gy in total<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) per RECIST 1.1 as assessed by BICR | To assess the efficacy in terms of PFS in PD-L1 High population | up to approximately 56 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | To assess the efficacy in terms of OS in all randomized patients and in PD-L1 High population until the date of death | up to approximately 72 months | 
| Progression free survival (PFS) per RECIST 1.1 as assessed by BICR | To assess the efficacy in terms of PFS in all randomized patients. | up to approximately 56 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced unresectable ESCC, PD-L1, Durvalumab