Efficacy of Perioperative Chemotherapy Plus PD-1 Antibody in the Locally Advanced Gastric Cancer

July 28, 2023 updated by: Rui-hua Xu, MD, PhD, Sun Yat-sen University

Perioperative Chemotherapy Plus PD-1 Antibody Compared With Perioperative Chemotherapy in the Locally Advanced Gastric Cancer: a Open-label, Phase 2 Randomised Controlled Trial

For locally advanced gastric cancer (cT3-4aN+M0), neoadjuvant chemotherapy can downstage T and N stage, increase the resectability of tumor, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric cancer could be a novel therapy to increase response rate and resectability 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 tolerability, safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced gastric cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Gastric cancer is one of the most common malignancies in China with incidence and mortality both ranking the 2nd among malignancies in China. Surgery is the only possible way to cure gastric cancer, however, over 80-90% of gastric cancer patients in China are in advanced stage. Locally advanced gastric cancer (cT3-4aN+M0) could be cured by multi-disciplinary therapies including surgery, chemotherapy and radiotherapy. Neoadjuvant chemotherapy can downstage T and N stage, increase the resectability of tumor, 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 gastric cancer could be a novel therapy to increase response rate and resectability 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 tolerability, safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced gastric cancer.

Study Type

Interventional

Enrollment (Actual)

108

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Written (signed) informed consent;
  2. Histologically CT/MRI confirmed cT3-4aN+M0 gastric adenocarcinoma;
  3. Consent to send tumor tissue from biopsy or resection for PD-L1, EBV, MSI detection;
  4. Female or male, 18-75 years;
  5. ECOG 0-1, no surgery contraindications;
  6. Physical condition and adequate organ function to ensure the success of abdominal surgery;
  7. Expected survival ≥3 months;
  8. Adequate hematological, liver, renal and coagulation function;

1) Platelet (PLT) count ≥100,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin (HbA1c) <7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min; 11) Thyroid stimulating hormone (TSH) ≤ULN; 12) Normal serum free thyroid hormone (T4); 13) Normal serum free triiodothyronine (T3); 14) Serum amylase ≤1.5×ULN; 15) Lipase ≤1.5×ULN.

9.Females of child bearing age must have a negative pregnancy test, and have to take contraception measures and avoid breast feeding during the study and for 3 months after the last dose; male subjects must agree to taken contraception measures during the study and for 3 months after the last dose.

Exclusion Criteria:

  1. Known allergy to study drug or excipients, or allergy to similar drugs;
  2. Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured localized tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ;
  3. Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment;
  4. Weight loss >20% within 2 weeks before recruitment;
  5. Unable to swallow study drug;
  6. Prior chemotherapy, radiotherapy, surgery for gastric cancer;
  7. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
  8. Prior therapy with tyrosine kinase inhibitor within 2 weeks.
  9. 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;
  10. Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
  11. Poorly controlled hypertension or diabetes;
  12. With bleeding tendency, or evident hemoptysis or other hemorrhagic events (e.g. gastrointestinal hemorrhage, hemorrhagic gastric ulcer) within 2 months prior to initiation of study treatment, or presence of hereditary or acquired bleeding or thrombotic tendency (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or current/long-term thrombolytic or anticoagulant therapy (except aspirin ≤100 mg/day);
  13. Present or history of any autoimmune disease;
  14. With active tuberculosis or receiving previous anti-tuberculosis therapy within one year;
  15. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;
  16. Pregnancy or breast feeding;
  17. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg or HBcAb positive, and HBV-DNA ≥2000 IU/ml (copies/ml)), or other severe infection requiring systemic antibiotic treatment, or unexplained body temperature >38.5℃ during screening period/before study treatment;
  18. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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 3 cycles, adjuvant chemotherapy for 5 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 Names:
  • XELODA
Experimental: 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 3 cycles, adjuvant chemotherapy for 5 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 Names:
  • XELODA
Drug: JS001
JS001, recombinant humanized anti-PD-1 monoclonal antibody for injection; 240mg ivdrip, d1, q3w.
Other Names:
  • PD-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TRG0/1
Time Frame: From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Pathological tumor regression grade 0/1
From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
R0 resection rate
Time Frame: From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Rate of microscopically margin-negative resection
From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
pCR
Time Frame: From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Pathological complete response
From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Recurrence free survival (RFS)
Time Frame: 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
The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented recurrence
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
Objective response rate (ORR)
Time Frame: 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
Defined as the proportion of patients whose tumors shrink for a certain period of time
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
Disease control rate (DCR)
Time Frame: 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]
Defined as the proportion of patients whose tumors shrink or remain stable for a certain period of time
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)
Time Frame: 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
The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Shanghai Junshi Bioscience Co., Ltd.

Investigators

  • Principal Investigator: Rui-hua Xu, MD,PhD, Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2019

Primary Completion (Actual)

June 27, 2022

Study Completion (Estimated)

October 5, 2024

Study Registration Dates

First Submitted

November 10, 2019

First Submitted That Met QC Criteria

January 30, 2020

First Posted (Actual)

January 31, 2020

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 28, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Neoadjuvant PD-1/LAGC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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