PD1 Combined With Chemotherapy for Adjuvant Treatment of Gastric Cancer

Phase 3

Active, not recruiting

• Conditions: Gastric or Esophagogastric Junction Adenocarcinoma
• Interventions: Biological: JS001/Placebo; Biological: JS001/placebo combine with Postoperative Adjuvant Chemotherapy

• Registration Number: NCT05180734
• Lead Sponsor: Shanghai Junshi Bioscience Co., Ltd.

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toxicity, disease recurrence, patient's withdrawal of consent, investigator's judgment that the patient needs to be withdrawn from the study treatment, or death, whichever comes first.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.

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Study Timeline

• Study First Submitted: 2021-11-08
• Study First Submitted QC: 2022-01-04
• Study First Posted: 2022-01-06
• Study Start: 2022-02-10
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-15
• Primary Completion: 2026-06-30
• Study Completion: 2028-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 878

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
JS001 240mg, Q3W with XELOX regimen or SOX regimen	JS001/Placebo	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.
Placebo combine with chemotherapy	JS001/placebo combine with Postoperative Adjuvant 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.

Primary Outcome Measures

Name	Time	Method
DFS in the PD-L1-positive population evaluated by the BICR	5 years	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.

Secondary Outcome Measures

Name	Time	Method
OS in the PD-L1-positive population	5 years	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.
DFS in the PD-L1-positive population evaluated by the investigator	5 years	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.
DFS in the ITT population evaluated by the BICR and investigator, respectively	5 years	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.
OS in the ITT population	5 years	To evaluate the OS for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the ITT population.
DFS rate at 3 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively	3 years	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.
DFS rate at 5 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively	5 years	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.
OS rate at 3 years in the PD-L1-positive population and the ITT population	3 years	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.
OS rate at 5 years in the PD-L1-positive population and the ITT population	5 years	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.
Blood trough concentration of toripalimab	Up to the 90 days from last dose of toripalimab	To evaluate the blood trough concentration of toripalimab
Immunogenicity of toripalimab	Up to the 90 days from last dose 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).

Trial Locations

Locations (71)

The First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu, Anhui, China

The Peple's Hospital of Chizhou; 🇨🇳 Chizhou, Anhui, China

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Hospital; 🇨🇳 Beijing, Beijing, China

Peking University People's hospital; 🇨🇳 Beijing, Beijing, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Cancer hospital; 🇨🇳 Beijing, Beijing, China

The first affiliated hospital of chongqing medical universit; 🇨🇳 Chongqing, Chongqing, China

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, Fujian, China

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