PD1 Combined With Chemotherapy for Adjuvant Treatment of Gastric Cancer

A Multicenter, Randomized, Double-Blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection Combined With Postoperative Adjuvant Chemotherapy Versus Placebo Combined With Postoperative Adjuvant Chemotherapy in Patients With Gastric or Esophagogastric Junction Adenocarcinoma After Radical Gastrectomy

This multicenter, randomized, double-blind phase III study intends to recruit about 878 patients, including PD-L1 positive 660 patients, who have received radical gastrectomy (R0 resection, D2 or more extended lymphadenectomy) with postoperative pathological stage IIB or III (AJCC Cancer Staging Manual, 8th Edition) gastric or EGJ adenocarcinoma to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric or Esophagogastric Junction Adenocarcinoma
• Intervention / Treatment: Biological: JS001/Placebo; Biological: JS001/placebo combine with Postoperative Adjuvant Chemotherapy

Detailed Description

"This is a multicenter, randomized, double-blind phase III study, plans to recruit 878 patients who received radical gastrectomy (R0, D2 or higher lymphadenectomy) with postoperative pathological stage II (T4aN0M0) or III (the 8th Edition American Joint Committee on Cancer [AJCC] Cancer Staging Manual) gastric adenocarcinoma and gastroesophageal junction adenocarcinoma, and the study intends to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.

Patients meeting the inclusion criteria will be 1:1 randomized into JS001-chemotherapy group and placebo-chemotherapy group. The random stratification factors include adjuvant chemotherapeutic regimens (XELOX versus SOX) and tumor anatomical sites (gastric adenocarcinoma versus gastroesophageal junction adenocarcinoma).

The study treatment will be initiated 4-6 weeks after surgery, and the investigator will select XELOX (Oxaliplatin + capecitabine) or SOX (Oxaliplatin + S-1, tegafur, gimeracil and oteracil potassium) as the adjuvant chemotherapeutic regimen given as 3-week cycles for up to 8 cycles based on each patient's condition; JS001/placebo will be given for up to 17 cycles after surgery, until intolerable toxicity, disease recurrence, patient's withdrawal of consent, investigator's judgment that the patient needs to be withdrawn from the study treatment, or death, whichever comes first.

Safety evaluation, including vital signs, ECOG score, physical examination and laboratory examinations, will be performed on a regular basis during the treatment.

This study will end after the main analysis node of DFS and unblinding for analysis are achieved, or 5 years after enrollment of the last patient, whichever comes first. The Sponsor is entitled to terminate the study at any time due to specific reasons (e. g, major safety issues, force majeure, etc.).

Radiological follow-up: tumor response evaluation will be performed once every 12 weeks ±7 days within the first 5 years after randomization, and once per year subsequently, until disease recurrence or death. When symptoms or signs of suspected recurrence/metastasis occur, the radiological evaluation can be performed at any time. Disease recurrence is defined as local recurrence or distant metastases with clear radiological evidence (CT or MRI).

Survival follow-up: it will be performed once every 12 weeks after disease recurrence, until patient's withdrawal of informed consent, loss to follow-up or death, whichever comes first.

Safety follow-up: adverse events will be closely followed up and recorded, until 60 days after the last dose of treatment or the end of study follow-up (death, loss to follow-up, withdrawal of consent form and the end of study), whichever comes first.

"

• Study Type: Interventional
• Enrollment (Actual): 878
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233300
      • The First Affiliated Hospital of Bengbu Medical College
    • Chizhou, Anhui, China
      • The Peple's Hospital of Chizhou
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100005
      • Beijing Hospital
    • Beijing, Beijing, China, 100000
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 510515
      • Beijing Cancer Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • The First Affiliated Hospital of Chongqing Medical Universit
  • Fujian
    • Fuzhou, Fujian, China, 350011
      • Fujian Provincial Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Gansu Provincial Cancer Hospital
    • Lanzhou, Gansu, China, 730000
      • Lanzhou University Second Hospital
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial People's Hospital
    • Lanzhou, Gansu, China, 750050
      • The First Hospital of Lanzhou University
    • Wuwei, Gansu, China, 733000
      • Wuwei Cancer Hospital of Gansu Province
  • Guandong
    • Guangzhou, Guandong, China, 510000
      • Guandong General Hospital
    • Guangzhou, Guandong, China, 510280
      • Zhujiang Hospital of Southern Medical University
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510095
      • Affiliated Cancer Hospital and Institute of Ghuangzhou Medical University
    • Shaoguan, Guangdong, China, 512099
      • Yuebei People's Hospital
    • Shenzhen, Guangdong, China, 518000
      • ShenZhen People's Hospital
    • Shenzhen, Guangdong, China, 518000
      • Peking University Shenzhen Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital
  • Guizhou
    • Zunyi, Guizhou, China, 563099
      • Affiliated Hospital of Zunyi Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China, 150086
      • The 2ed Affiliated Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
  • Henan
    • Luoyang, Henan, China, 450052
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Zhengzhou, Henan, China, 450052
      • the First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
    • Xiangyang, Hubei, China, 441021
      • Xiangyang Central Hospital
    • Yichang, Hubei, China, 443008
      • Yichang Central People's Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China, 410031
      • Hunan Cancer Hopital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213004
      • The First People's Hospital of Changzhou
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Cancer Hospital
    • Nantong, Jiangsu, China, 226006
      • Nantong Tumor Hospital
    • Wuxi, Jiangsu, China, 214001
      • The Second People's Hospital of Wuxi
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • Jiangmen Central Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital of Jilin University
  • Liaoning
    • Shengyang, Liaoning, China, 110000
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110000
      • Liaoning Cancer Hospital & Institute
  • Ningxia
    • Yinchuan, Ningxia, China, 750000
      • General Hospital of Ningxia Medical University
  • Qinghai
    • Xining, Qinghai, China, 810000
      • Qinghai University Affiliated Hosptial
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Linyi, Shandong, China, 276002
      • LinYi Cancer Hospital
    • Qingdao, Shandong, China, 266003
      • The affiliated hospital of Qingdao university
    • Qingdao, Shandong, China, 266042
      • Qingdao central medical group
  • Shangdong
    • Jinan, Shangdong, China, 250012
      • Jinan Central Hospital
    • Jinan, Shangdong, China, 250031
      • Shandong Provincial Hospital
    • Jining, Shangdong, China, 272007
      • Affiliated Hospital of Jining Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China, 030012
      • Shanxi Provincial People's Hospital
    • Xian, Shanxi, China, 710000
      • Tangdu Hospital, Air Force Military Medical University
    • Xian, Shanxi, China, 710000
      • Xijing hospital, Air force Military Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Cancer Hospital
    • Suining, Sichuan, China, 629000
      • Suining Central Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Cancer Hospital affiliated to Xinjiang Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Zhejiang Medical University
    • Jiaxing, Zhejiang, China, 314001
      • The First Hospital of Jiaxing
    • Wenzhou, Zhejiang, China, 325024
      • The Second Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

INCLUSION CRITERIA

1. Age 18-75 years.
2. No residual tumor (R0) after D2 or greater lymphadenectomy through laparotomy.
3. According to the definition of the 8th edition of the AJCC Cancer Staging Manual, patients with gastric adenocarcinoma confirmed by histopathology, pathological stage II (T4aN0M0) and stage III, including gastroesophageal junction adenocarcinoma (GEJ) patients.
4. Patients need to provide sufficient formalin-fixed paraffin-embedded (FFPE) neoplasm tissue specimens or sections that are confirmed to be PD-L1 positive (CPS ≥ 1) by lab test at the central laboratory.
5. ECOG performance status 0-1.
6. No metastasis or recurrence as radiologically confirmed.
7. Patients must have adequate organ function as assessed in the laboratory tests.
8. Patients must provide informed consent for this study, and sign the written informed consent form voluntarily before the initiation of the study, and are willing and able to comply with the scheduled visits, treatment plan, laboratory examinations and other study procedures in the study.
9. Female patients of childbearing age must take a serum pregnancy test within 7 days before randomization with negative results, and agree to adopt reliable and effective contraceptive methods during the study.

EXCLUSION CRITERIA

1. Previous use of non-surgical therapy (e.g., radiotherapy, chemotherapy, hormone therapy) for gastric adenocarcinoma.
2. Having liver, peritoneal or other distant metastasis.
3. Having malignant tumors other than gastric adenocarcinoma within 5 years before randomization.
4. Pevious treatment targeting PD-1 receptor or its ligand PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptor;
5. Previous history of serious allergy to monoclonal antibody or other biological preparations.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS001 240mg, Q3W with XELOX regimen or SOX regimen; JS001 240mg, will be intravenously administered once every 3 weeks, until 17 cycles XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W. SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.	Biological: JS001/Placebo; JS001/placebo combine with Postoperative Adjuvant Chemotherapy; Other Names: Postoperative Adjuvant Chemotherapy
Placebo Comparator: Placebo combine with chemotherapy; XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W. SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.	Biological: JS001/placebo combine with Postoperative Adjuvant Chemotherapy; JS001/placebo combine with Postoperative Adjuvant Chemotherapy; Other Names: Postoperative Adjuvant Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS in the PD-L1-positive population evaluated by the BICR	To evaluate the disease-free survival (DFS) by the blind independent central review (BICR) for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in PD-L1-positive patients with gastric or GEJ adenocarcinoma after radical gastrectomy.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS in the PD-L1-positive population	To evaluate the OS for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in PD-L1-positive patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.	5 years
DFS in the PD-L1-positive population evaluated by the investigator	To evaluate the disease-free survival (DFS) by the investigator for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in PD-L1-positive patients with gastric or GEJ adenocarcinoma after radical gastrectomy.	5 years
DFS in the ITT population evaluated by the BICR and investigator, respectively	To evaluate the disease-free survival (DFS) by the blind independent central review (BICR) and investigator,respectively, for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the ITT population.	5 years
OS in the ITT population	To evaluate the OS for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the ITT population.	5 years
DFS rate at 3 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively	To evaluate the disease-free survival (DFS) rate at 3 years by the BICR and investigator, respevtively, for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the PD-L1-positive population and the ITT population.	3 years
DFS rate at 5 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively	To evaluate the disease-free survival (DFS) rate at 5 years by the BICR and investigator, respevtively, for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the PD-L1-positive population and the ITT population.	5 years
OS rate at 3 years in the PD-L1-positive population and the ITT population	To evaluate the OS rate at 3 years for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the PD-L1-positive population and the ITT population.	3 years
OS rate at 5 years in the PD-L1-positive population and the ITT population	To evaluate the OS rate at 5 years for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the PD-L1-positive population and the ITT population.	5 years
Immunogenicity of toripalimab	To evaluate the incidence and titer of anti-drug antibody (ADA) of toripalimab, and further analyze ADA-positive samples for the presence of Neutralising antibodies (Nab).	Up to the 90 days from last dose of toripalimab
Blood trough concentration of toripalimab	To evaluate the blood trough concentration of toripalimab	Up to the 90 days from last dose of toripalimab

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma
• Other Study ID Numbers: JS001-045-III-GC

Drug and device information, study documents

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