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

Overview

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).

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 30, 2025

Detailed Description

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 all randomized patients (intent-to-treat [ITT] population) and PFS in patients with PD-L1 high tumors (PD-L1 High population).

Interventions

  • Drug: Durvalumab
    • Durvalumab intravenous infusion
  • Drug: Placebo
    • Durvalumab matching placebo for intravenous infusion
  • Drug: cisplatin + fluorouracil
    • cisplatin + fluorouracil, as per Standard of Care
  • Drug: cisplatin + capecitabine
    • cisplatin + capecitabine, as per Standard of Care
  • Radiation: Radiation
    • 50-64Gy in total

Arms, Groups and Cohorts

  • Experimental: Arm 1: Durvalumab + definitive CRT
    • Durvalumab + concurrent chemoradiation
  • Placebo Comparator: Arm 2: Placebo + definitive CRT
    • Placebo + concurrent chemoradiation

Clinical Trial Outcome Measures

Primary Measures

  • Progression free survival (PFS) per RECIST 1.1 as assessed by BICR
    • Time Frame: up to approximately 56 months
    • To assess the efficacy in terms of PFS in all randomized patients and in patients with PD-L1 High tumors until disease progression

Secondary Measures

  • Overall survival (OS)
    • Time Frame: up to approximately 72 months
    • To assess the efficacy in terms of OS in all randomized patients and in patients with PD-L1 High tumors until the date of death

Participating in This Clinical Trial

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 and has been deemed suitable for definitive chemoradiation therapy.
  • Patients with at least 1 lesion that qualifies as a RECIST 1.1 Target Lesion at baseline.
  • 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, including but not limited to, chemotherapy and/or radiation therapy, immunotherapy, and investigational agents.
  • 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 130 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AstraZeneca
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Luhua Wang, MD, Principal Investigator, Cancer Hospital of Chinese Academy of Medical Science
  • Overall Contact(s)
    • AstraZeneca Clinical Study Information Center, 1-877-240-9479, information.center@astrazeneca.com

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