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

NCT04744649 | Unknown Phase 2 DMC

• 1 other identifier: NICE
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Gastric Cancer; Stomach Neoplasm

Keywords

Gastric Cancer; Esophagogastric Junction Cancer; Immunotherapy and Chemotherapy; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Major pathologic response (MPR)

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

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 14 weeks

Secondary Outcomes (5)

• Disease-free survival (DFS)

  From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

• Overall survival(OS)

  From date of randomization until the date of first documented date of death from any cause, assessed up to 36 months

• pCR

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 14 weeks

• R0 resection rate

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 14 weeks

• Adverse event incidence rate

  Patients will be assessed for adverse events throughout the study at every visit during treatment and at 3-month follow-up visit (3 months after treatment ends)

Study Arms (3)

Control group

ACTIVE COMPARATOR

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.

Drug: XELOX or SOX

Experimental group

EXPERIMENTAL

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.

Drug: JS001+XELOX or SOX

Exploratory group

OTHER

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.

Drug: JS001+XELOX or SOX

Interventions

XELOX or SOX DRUG

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

Also known as: Control group

Control group

JS001+XELOX or SOX DRUG

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

Also known as: Experimental group and Exploratory group

Experimental group; Exploratory group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written (signed) informed consent;
• Age ≥ 18 years and ≤75 years.
• Confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination.
• Imaging (CT/MRI) and diagnostic laparoscopy confirmed at the stage of cT3/4a Nx or T2 N+, M0(AJCC 8th) before randomization.
• confirmed by immunohistochemistry (IHC) staining or genetic and transcriptional profiling detection to meet one of the following conditions:
• Combined positive score (CPS) of PD-L1 protein expression ≥5.
• Epstein-Barr virus-positive (EBV(+)).
• mismatch repair-deficient (dMMR).
• Microsatellite instability-high (MSI-H)
• The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1
• Expected survival period ≥ 12 weeks
• The main organ function meets the following criteria within 7 days before treatment:
• Hemoglobin (Hb) level ≥9.0 g/dl
• Neutrophil count (ANC)≥1.5×l09/L
• Platelet (PLT) ≥100×109/L

You may not qualify if:

• Confirmed at stage IV (AJCC 8th) or unresectable by investigator before randomization.
• Prior chemotherapy, radiotherapy, surgery immunotherapy or molecular targeted therapy for gastric cancer;
• Patients who have HER2 positive confiemed with IHC3+ or IHC2+ and FISH positive
• Patients are allergic to study medication and its ingredients
• Patients with a history of following treatments:
• Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent
• Prior therapy with tyrosine kinase inhibitor within 2 weeks.
• Patients who have participated in other clinical trials of anti-tumor drugs within four weeks
• Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
• Concurrent medical condition requiring the use of cortisol (\>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent for replacement therapy
• Patients have experienced or currently has other malignancies within 5 years.
• Patients have an active or history of autoimmune disease that may recur or require immunosuppressive drugs within 2 weeks or less or during the study. Or have a history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation
• Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.
• Within 2 weeks or 2 weeks before randomization, patients have an active or uncontrollable infection that requires systemic antibiotic treatment
• Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (10)

Fujian Provincial Hospital

Fuzhou, Fujian, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

NOT YET RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510-515, China

RECRUITING

The six affiliated hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510515, China

RECRUITING

Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,

Guangzhou, Guangdong, China

RECRUITING

Mao ming people's hospital

Maoming, Guangdong, China

NOT YET RECRUITING

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

RECRUITING

The Eighth Affiliated Hospital, Sun Yat-Sen University

Shenzhen, Guangdong, China

NOT YET RECRUITING

Zhongshan People's Hospital

Zhongshan, Guangdong, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

NOT YET RECRUITING

Related Publications (1)

• Zhao L, Liu H, Yu J, Yuan S, Liang H, Wang W, Jiang J, Yu L, Liang L, Chen Z, Chen X, Zhong X, Zheng Y, Li F, Lin T, Zhao M, Chen T, Chen H, Hu Y, Li G. Efficacy and safety of neoadjuvant toripalimab plus chemotherapy in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma (NICE): a multicentre, single-arm, exploratory phase 2 study. EClinicalMedicine. 2025 Aug 12;87:103421. doi: 10.1016/j.eclinm.2025.103421. eCollection 2025 Sep.

  PMID: 40838201 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

XELOX; Control Groups

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Guoxin Li, M.D., Ph.D.

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

• Liying Zhao, M.D., Ph.D.

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+86 13802771450; gzliguoxin@163.com

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

CONTACT

+86 15626452302; xinhuachen03@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: January 23, 2021
• First Posted: February 9, 2021
• Study Start: March 12, 2021
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (10)