HX008 Plus Irinotecan Versus Placebo Plus Irinotecan as Second-line Treatment in Advanced Gastric Cancer

A Randomized, Double-blinded, Multicenter, Phase III Clinical Study of HX008 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) Plus Irinotecan Versus Placebo Plus Irinotecan as Second-line Treatment in Advanced Gastric Cancer

This is a randomized, double-blinded, multicenter study to evaluate the efficacy and safety of HX008 injection combined with irinotecan versus placebo combined with irinotecan as second-line therapy in patients with adcanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have had tumor progression after first-line treatment with platinum and/or fluropyrimidine therapy.

Study Overview

• Status: Recruiting
• Conditions: Stomach Cancer
• Intervention / Treatment: Drug: HX008; Drug: Irinotecan Hydrochloride Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 560
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jing Huang, MD; Phone Number: 010-87788113; Email: huangjingwg@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Cancer Hospital
      • Contact: Yifu He
    • Hefei, Anhui, China, 230001
      • Recruiting
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100032
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Lin Zhao
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital, Chinese Academy of Medical Sciences
      • Contact: Jing Huang, MD; Email: huangjingwg@163.com
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chaoyang Hospital, Capital Medical University
      • Contact: Guangyu An
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: Baoshan Cao
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 102206
      • Recruiting
      • Peking University Internationale Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Recruiting
      • Chongqing University Cancer Hospital
      • Contact: Weiqing Chen
  • Fujian
    • Xiamen, Fujian, China, 350000
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Rongbo Lin
  • Gansu
    • Wuwei, Gansu, China, 350000
      • Recruiting
      • Gansu Wuwei Tumor Hospital
      • Contact: Rongbo Lin
  • Guangdong
    • Guangzhou, Guangdong, China, 510095
      • Not yet recruiting
      • Affiliated Cancer Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 528403
      • Not yet recruiting
      • Zhongshan People's Hospital
    • Shenzhen, Guangdong, China, 518035
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Shubin Wang
    • Shenzhen, Guangdong, China, 518117
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
      • Contact: Chunxia Du
  • Guangxi
    • Naning, Guangxi, China, 530021
      • Recruiting
      • Guangxi Medical University Cancer Hospital
      • Contact: Zhihui Liu
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510080
      • Not yet recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Sheng Ye
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Shengmian Li
    • Shijiazhuang, Hebei, China, 050051
      • Recruiting
      • The First Hospital Of Hebei Medical University
      • Contact: Na Li
    • Shijiazhuang, Hebei, China, 071000
      • Recruiting
      • Affiliated Hospital of Hebei University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Recruiting
      • The Affiliated Cancer Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 471000
      • Recruiting
      • The First Affiliated Hospital of Henan Science&Technology University
    • Zhengzhou, Henan, China, 540003
      • Recruiting
      • Henan Provincial People's Hospital
      • Contact: Shundong Cang
  • Hunan
    • Changsha, Hunan, China, 410200
      • Recruiting
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410000
      • Recruiting
      • The Second Xiangya Hospital of Cancer South University
      • Contact: Xianling Liu
    • Changsha, Hunan, China, 410000
      • Not yet recruiting
      • Xiangya Hospital, Central South University
      • Contact: Shan Zeng
  • Inner Mongolia
    • Huhhot, Inner Mongolia, China, 010000
      • Recruiting
      • The Affiliated People's Hospital of Inner Mongolia Medical University
      • Contact: Zhenping Wen
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Recruiting
      • Changzhou Cancer Hospital
      • Contact: Yang Ling
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • NanJing Drum Tower Hospital
      • Contact: Yang Yang
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Jiangsu Provincial Hospital
      • Contact: Lingjun Zhu
    • Nanjing, Jiangsu, China, 210009
      • Not yet recruiting
      • Zhongda Hospital Southeast Universtiy
      • Contact: Cailian Wang
    • Nantong, Jiangsu, China, 226006
      • Recruiting
      • Nantong Tumor Hospital
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The Second Affiliated Hospital of Soochow University
      • Contact: Zhixiang Zhuang
    • Xuzhou, Jiangsu, China, 221009
      • Recruiting
      • XuZhou Central Hospital
      • Contact: Yuan Yuan
    • Yangzhou, Jiangsu, China, 225000
      • Recruiting
      • Yangzhou First People's Hospital
      • Contact: Jiandong Tong
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital Of NanChang University
      • Contact: Xiaojun Xiang
    • Nanchang, Jiangxi, China, 330029
      • Recruiting
      • Jiangxi Cancer Hospital
      • Contact: Yiye Wan
  • Jilin
    • Changchun, Jilin, China, 130000
      • Not yet recruiting
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130000
      • Recruiting
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Not yet recruiting
      • The First Hospital of China Medical University
      • Contact: Yunpeng Liu
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • Liaoning Cancer Hospital
  • Ningxia
    • Yinchuan, Ningxia, China, 750001
      • Recruiting
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
      • Contact: Bo Liu
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Weibo Wang
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • The Affiliated Hospital of Qingdao University
    • Yantai, Shandong, China, 264000
      • Not yet recruiting
      • Yantai Yuhuangding Hospital
      • Contact: Ping Sun
  • Shanghai
    • Shanghai, Shanghai, China, 200233
      • Not yet recruiting
      • Shanghai Sixth People's Hospital
      • Contact: Zan Shen
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai General Hospital
      • Contact: Hongxia Wang
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Shanxi Cancer Hospital
    • Xi'an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Enxiao Li
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Sichuan Cancer hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Recruiting
      • Tianjin Medical University General Hospital
  • Wuhan
    • Hubei, Wuhan, China, 430000
      • Recruiting
      • Hubei Cancer Hospital
      • Contact: Xinjun Liang
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Recruiting
      • The First Affiliated Hospital of Xinjiang Medical University
      • Contact: Wenran Wang
    • Urumqi, Xinjiang, China, 830000
      • Not yet recruiting
      • Xinjiang Medical University Cancer Hospital
      • Contact: Yong Tang
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Not yet recruiting
      • Yunnan cancer hospital
      • Contact: Qing Bi
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer hospital
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial people's hospital
      • Contact: Liqin Lu
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Yi Zheng
    • Hangzhou, Zhejiang, China, 310016
      • Recruiting
      • Sir Run Run Shaw Hospital, Medical School of Zhejiang University
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Zhiming Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Understood and signed an informed consent form.
• Age ≥ 18 and ≤ 75 years old, male or female.
• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma of stomach or the esophagogastric junction (GEJ).
• Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing platinum and/or fluoropyrimidine therapy.
• Willing to provide tissue for PD-L1 biomarker analysis.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Score.
• Life expectancy ≥ 3 months.
• Has adequate organ function.
• Female participants of childbearing potential should have a negative pregnancy within 72 hours before the randomization. Male and female participants should agree to use an adequate method of contraception during the experiment and 1 year after the last administration of the test drugs.

Exclusion Criteria:

• Has squamous cell or undifferentiated gastric cancer.
• Diagnosed additional maliganancy within 3 years prior to randomization with the expection of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin,curatively resected in situ cervival or non-muscle invasive bladder cancers.
• Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy,radiation therapy or targeted small molecular therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to a previously administrated agent.
• Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-CTLA-4 agents.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has uncontrolled ascites, pleural effusion, or pericardial effusion.
• Has active autoimmune disease that has required systemic treatment in past 2 years.
• Has received a major surgery within 4 weeks prior to randomization.
• Has received system treatment with corticosteroids (dose >10mg/day prednison or other therapeutic hormones) within 2 weeks prior to the first dose of trial treatment.
• Has incomplete intestinal obstruction, active gastrointestinal hemorrhage and perforation.
• Has a history of non-infectious pneumonitis that required steriods or has current pneumonitis.
• Has any serious and/or uncontrolled disease.
• Has active viral infection.
• Has received a live vaccine within 30 days prior to the first dose of trial treatment.
• Has participated in other anticancer drug clinical trials within 4 weeks.
• According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HX008 plus Irinotecan; Participants recieve HX008 200 mg intravenous (IV) every 3 weeks (Q3W) plus irinotecan 160 mg/m², IV, Q2W.	Drug: HX008; 200 mg administered as IV infusion on Day 1 of each 21-day cycle.; Drug: Irinotecan Hydrochloride Injection; 160 mg/m² administered as IV infusion on Day 1 of each 14-day cycle.
Placebo Comparator: Placebo plus Irinotecan; Participants recieve placebo intravenous (IV) every 3 weeks (Q3W) plus irinotecan 160 mg/m², IV, Q2W.	Drug: Irinotecan Hydrochloride Injection; 160 mg/m² administered as IV infusion on Day 1 of each 14-day cycle.; Drug: Placebo; Administered as IV infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in All Participants	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported here for all participants in the experimental arm and placebo comparator arm.	Up to approximately 36 months
Overall Survival (OS) in Participants With PD-L1 CPS≥1	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported here for all participants in the experimental arm and placebo comparator arm with PD-L1 CPS≥1.	Up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 assessed by investigators or death due to any cause, whichever occurs first.	Up to approximately 36 months
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants who have a complete response (CR) or a partial response (PR), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators.	Up to approximately 36 months
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	DCR was defined as the percentage of participants who have a CR or a PR or a stable disease (SD), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators.	Up to approximately 36 months
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	DOR was defined as the time from the first documented evidence of a response of CR or PR, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators.	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Taizhou Hanzhong biomedical co. LTD

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Anticipated): August 10, 2023
• Study Completion (Anticipated): August 10, 2023

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: HX008-III-GC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No