Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Capecitabine

Immunomodulating Agents

Oxaliplatin

Immunoglobulins

Fluorouracil

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

The patients with combined positive score (CPS) of PD-L1 protein expression≥5 were randomised to control group(N=40), will receive the neoadjuvant regime of XELOX or SOX.

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1. Oxaliplatin: 130mg/m2, iv drip for 2h, d1, q3w; S-1:40\~60mg Bid, d1\~14, q3w; Capecitabine: 1000mg/m2 Bid, d1-14, q3w; Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

The patients with combined positive score (CPS) of PD-L1 protein expression≥5 were randomised to experimental group(N=40), will receive the neoadjuvant regime of JS001+XELOX or SOX.

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1. JS001: 240mg, ivdrip, d1, q3w; S-1:40\~60mg Bid, d1\~14, q3w; Capecitabine: 1000mg/m2 Bid, d1-14, q3w; Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

All the patients of Epstein-Barr virus-positive (EBV(+)) \[N=15\]or mismatch repair-deficient (dMMR)/ microsatellite instability-high (MSI-H)\[N=15\] , will be assigned to exploratory group, and will receive the neoadjuvant regime of JS001+XELOX or SOX.

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1. JS001: 240mg, ivdrip, d1, q3w; S-1:40\~60mg Bid, d1\~14, q3w; Capecitabine: 1000mg/m2 Bid, d1-14, q3w; Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1

Oxaliplatin: 130mg/m2, iv drip for 2h, d1, q3w;

S-1:40\~60mg Bid, d1\~14, q3w;

Capecitabine: 1000mg/m2 Bid, d1-14, q3w;

Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

Drug: Oxaliplatin Oxaliplatin: 130mg/m2，iv drip for 2h，d1, q3w

Drug: S1 S-1: 40\~60mg Bid，d1\~14, q3w

Drug: Capecitabine Capecitabine: 1000mg/m2 Bid, d1-14, q3w Other Name: XELODA

JS001: 240mg, ivdrip, d1, q3w;

S-1:40\~60mg Bid, d1\~14, q3w;

Capecitabine: 1000mg/m2 Bid, d1-14, q3w;

Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

Drug: JS001 JS001, recombinant humanized anti-PD-1 monoclonal antibody for injection; 240mg ivdrip, d1, q3w.

Other Name: PD-1 antibody

Drug: Oxaliplatin Oxaliplatin: 130mg/m2,iv drip for 2h, d1, q3w

Drug: S1 S-1: 40\~60mg Bid,d1\~14, q3w

Drug: Capecitabine Capecitabine: 1000mg/m2 Bid, d1-14, q3w Other Name: XELODA

XELOX or SOX

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1

JS001: 240mg, ivdrip, d1, q3w;

S-1:40\~60mg Bid, d1\~14, q3w;

Capecitabine: 1000mg/m2 Bid, d1-14, q3w;

Neoadjuvant chemotherapy for 4 cycles, adjuvant chemotherapy for 4 cycles.

Drug: JS001 JS001, recombinant humanized anti-PD-1 monoclonal antibody for injection; 240mg ivdrip, d1, q3w.

Other Name: PD-1 antibody

Drug: Oxaliplatin Oxaliplatin: 130mg/m2,iv drip for 2h, d1, q3w

Drug: S1 S-1: 40\~60mg Bid,d1\~14, q3w

Drug: Capecitabine Capecitabine: 1000mg/m2 Bid, d1-14, q3w Other Name: XELODA

JS001+XELOX or SOX

Guoxin Li, M.D., Ph.D.

Xinhua Chen, M.D., Ph.D.

Fangqin Xue

Jun You

Liying Zhao, M.D., Ph.D.

Lei Lian, MD

Wei Wang

Dingming Li

Guoqing Lv

Xiaobin Wu

Hong Chen

Kuan Wang

For locally advanced esophagogastric junction and gastric cancer (cT3-4aNxM0 or cT2N+M0), neoadjuvant chemotherapy can downstage T and N stage,treated distant micrometastases early before local therapy has begun, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced esophagogastric junction and gastric cancer could be a novel therapy to increase response rate and reduce recurrence rate. JS001 in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is a multi-center, open-label, randomized phase II clinical trial to evaluate safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced esophagogastric junction and gastric cancer. Differences in gut microbiome and tumor immune microenvironment were detected to screen people who were more sensitive to immunotherapy.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and a substantial global health burden. Surgery is the only possible way to cure gastric cancer, however, more than 80% of the Chinese patients are diagnosed at advanced stages. Locally advanced esophagogastric junction and gastric cancer (cT3-4aNxM0 or cT2N+M0) could be cured by multi-disciplinary therapies including surgery, chemotherapy and radiotherapy. Neoadjuvant chemotherapy can downstage T and N stage, treated distant micrometastases early before local therapy has begun, and finally improve the long-term survival. However, the therapeutic effects remain unsatisfactory. PD-1 antibody has demonstrated its efficacy in metastatic gastric cancer and has been proved to be effective in neoadjuvant setting in lung cancer and melanoma. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced esophagogastric junction and gastric cancer could be a novel therapy to increase response rate and reduce recurrence rate. JS001 in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is a multi-center, open-label, randomized phase II clinical trial to evaluate safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced esophagogastric junction and gastric cancer. Differences in gut microbiome and tumor immune microenvironment were detected to screen people who were more sensitive to immunotherapy.

Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial

Efficacy and Safety of Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer : a Open-label, Phase 2 Randomised Controlled Trial (NICE Trial)

We will share Study Protocol and Statistical Analysis Plan (SAP)

It is defined as residual tumors less than 10% after neoadjuvant immunotherapy and(or) chemotherapy

The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented recurrence.

Pathological complete response after neoadjuvant immunotherapy and(or) chemotherapy

Rate of microscopically margin-negative resection

Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v4.03

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial	NCT04744649	Gastric Cancer Stomach Neoplas...	XELOX or SOX JS001+XELOX or ...	18 Years - 75 Years	Nanfang Hospital, Southern Medical University
Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial	NCT04744649	Gastric Cancer Stomach Neoplas...	XELOX or SOX JS001+XELOX or ...	18 Years - 75 Years	Nanfang Hospital, Southern Medical University

Spots Global Cancer Trial Database for js001+xelox or sox