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

Capecitabine

Immunomodulating Agents

Oxaliplatin

Antibodies, Bispecific

Immunoglobulins

Antimetabolites

Neoadjuvant Immunotherapy and Chemotherapy：Cadonilimab+Oxaliplatin+Capecitabine, every 3 weeks for 3 cycles;

Adjuvant chemotherapy： Oxaliplatin+Capecitabine, every 3 weeks for 3-5 cycles;

Cadonilimab

Guoxin Li, M.D., Ph.D

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

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

For locally advanced esophagogastric junction and gastric cancer, neoadjuvant chemotherapy can downstage T and N stage,treated distant micrometastases early , 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.Cadonilimab, a tetravalent bispecific antibody targeting PD-1 and CTLA-4, is designed to retain the efficacy benefit of combination of PD-1 and CTLA-4 and improve on the safety profile of the combination therapy. The aim of this study is to evaluate the efficacy and safety of cadonilimab Plus Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer.

Locally advanced esophagogastric junction and gastric cancer 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.Cadonilimab (AK104), a novel bispecific antibody simultaneously targeting PD-1 and CTLA-4, was designed to boost anti-tumor activity with a favorable safety profile.This study was a single arm, open-label clinical study to evaluate the efficacy and safety of combination with Cadonilimab and Chemotherapy for neoadjuvant treatment of resectable locally advanced adenocarcinoma of the gastro-esophageal junction.

Neoadjuvant Cadonilimab Plus Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial

Efficacy and Safety of Neoadjuvant Cadonilimab and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer : a Prospective, Open-label, Single-Arm Phase II Study

Pathological complete response (pCR) rate is defined as the proportion of participants whose tumor in the stomach and lymph node completely disappeared, as determined by a pathologist.

Major pathological response (MPR) rate is defined as the proportion of participants whose percentage of residual tumor in the stomach and lymph node decreased to \< 10%, as determined by a pathologist

Rate of microscopically margin-negative resection

defined as the percentage of participants who achieve a best overall response of complete response or partial response assessed according to mRECIST v1.1 for assessment of response in malignant pleural mesothelioma.

defined as the percentage of participants who achieve a best overall response of complete response, partial response, or stable disease assessed according to mRECIST v1.1 for assessment of response in malignant pleural mesothelioma.

3 years disease-free survival (DFS) rate is defined as proportion of participants who have no recurrence or metastasis after 3 years of radical treatment

defined as the time between the date of first dose of study drug and the date of death due to any cause.

Nanfang Hospital, Southern Medical University

Antibodies, Monoclonal

Fluorouracil

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

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

Fangqin Xue

Jun You

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

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
Neoadjuvant Cadonilimab Plus Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial	NCT06310473	Gastric Cancer Esophagogastric...	Cadonilimab Oxaliplatin Capecitabine	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
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

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