Clinical trial NCT05180734: PD1 Combined With Chemotherapy for Adjuvant Treatment of Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gastric or Esophagogastric Junction Adenocarcinoma
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2022-01-06
Enrollment: 878
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

"

Eligibility criteria: 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.

Primary outcomes:
measure: DFS in the PD-L1-positive population evaluated by the BICR
timeFrame: 5 years
Secondary outcomes:
measure: OS in the PD-L1-positive population
timeFrame: 5 years
measure: DFS in the PD-L1-positive population evaluated by the investigator
timeFrame: 5 years
measure: DFS in the ITT population evaluated by the BICR and investigator, respectively
timeFrame: 5 years
measure: OS in the ITT population
timeFrame: 5 years
measure: DFS rate at 3 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively
timeFrame: 3 years
measure: DFS rate at 5 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively
timeFrame: 5 years
measure: OS rate at 3 years in the PD-L1-positive population and the ITT population
timeFrame: 3 years
measure: OS rate at 5 years in the PD-L1-positive population and the ITT population
timeFrame: 5 years
measure: Immunogenicity of toripalimab
timeFrame: Up to the 90 days from last dose of toripalimab
measure: Blood trough concentration of toripalimab
timeFrame: Up to the 90 days from last dose of toripalimab
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Chizhou
country: China
facility: The Peple's Hospital of Chizhou
state: Anhui
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Chongqing
country: China
facility: The first affiliated hospital of chongqing medical universit
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial People's Hospital
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Lanzhou
country: China
facility: The first Hospital of Lanzhou University
state: Gansu
city: Wuwei
country: China
facility: Wuwei Cancer Hospital of Gansu Province
state: Gansu
city: Guangzhou
country: China
facility: Guandong General Hospital
state: Guandong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guandong
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and Institute of Ghuangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Ha'erbin
country: China
facility: The 2ed Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan cancer hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hopital
state: Hunan
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu cancer hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: The Second People's Hospital of Wuxi
state: Jiangsu
city: Nanchang
country: China
facility: Jiangmen Central Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The first Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Shengyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: LiaoNing Cancer Hospital & Institute
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Xining
country: China
facility: Qinghai University Affiliated Hosptial
state: Qinghai
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Qingdao
country: China
facility: Qingdao central medical group
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shangdong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shangdong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shangdong
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan university
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Xian
country: China
facility: Tangdu hospital, Air force Military Medical University
state: Shanxi
city: Xian
country: China
facility: Xijing hospital, Air force Military Medical University
state: Shanxi
city: Chengdu
country: China
facility: SiChuan Cancer Hospital
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Urumqi
country: China
facility: Cancer Hospital affiliated to Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The first affiliated hospital of Zhejiang medical university
state: Zhejiang
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing
state: Zhejiang
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: