Gastric Cancer (GC), Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Radiotherapy, CAPOX, SHR-1701, Immunotherapy, Chemotherapy, Unresectable gastric cancer, Metastatic gastric cancer, Locally advanced gastric cancer, PD-L1/TGF-β bispecific antibody
Brief summary
Gastric Cancer is one of the leading causes of cancer-related death worldwide, and patients with unresectable locally advanced or metastatic disease have a poor prognosis. This study aims to evaluate the safety and efficacy of radiotherapy combined with CAPOX and SHR-1701, a PD-L1/TGF-β bispecific antibody, in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. By improving local tumor control and enhancing systemic antitumor activity, this study seeks to increase the opportunity for curative-intent resection and improve survival outcomes in patients with advance gastric cancer.
Detailed description
The investigators are conducting a clinical research study to evaluate the efficacy and safety of radiotherapy combined with CAPOX and SHR-1701 for patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The study hypothesizes that radiotherapy combined with CAPOX and SHR-1701, a PD-L1/TGF-β bispecific antibody, may improve clinical outcomes compared with the current standard first-line treatment. The primary objective is to evaluate progression-free survival (PFS). Secondary objectives include objective response rate (ORR), overall survival (OS), local control rate (LCR), R0 resection rate, pathological complete response (pCR), major pathological response (MPR), treatment-related adverse events, and quality of life. The trial will enroll 60 participants across multiple study centers. Eligible participants will receive radiotherapy combined with CAPOX and SHR-1701, followed by SHR-1701 maintenance therapy when appropriate. Exploratory analyses will evaluate potential biomarkers associated with treatment response and survival. This study aims to provide a safe and effective first-line treatment strategy for patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
Interventions
DRUGCOPOX
CAPOX consists of oxaliplatin (130 mg/m²) administered intravenously on day 1 and capecitabine (1,000 mg/m²) administered orally twice daily on days 1-14 of each 21-day cycle (Q3W) according to the study protocol.
RADIATIONRadiotherapy
Radiotherapy will be delivered to the primary tumor (30 Gy in 10 fractions) and metastatic lesions (25-35 Gy in 5-7 fractions), with the dose determined according to the location, number, and size of metastatic lesions and normal tissue dose constraints in accordance with the study protocol.
BIOLOGICALSHR-1701
SHR-1701 (1800 mg) will be administered intravenously on day 1 or each 21-day cycle (Q3W) according to the study protocol.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will receive induction CAPOX plus SHR-1701 followed by radiotherapy and subsequent combination therapy according to the study protocol.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged 18 to 75 years. 2. Histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma. 3. Unresectable locally advanced or metastatic gastric cancer, with primary and metastatic lesions amenable to radiotherapy (excluding patients with brain metastases or extensive metastatic disease). 4. HER2-negative disease. 5. ECOG performance status of 0-1. 6. At least one measurable lesion according to RECIST version 1.1. 7. Adequate organ function, including: * Hemoglobin ≥90 g/L; * White blood cell count ≥3.5 × 10⁹/L; * Absolute neutrophil count ≥1.5 × 10⁹/L; * Platelet count ≥100 × 10⁹/L; * Serum creatinine ≤1.0 × upper limit of normal (ULN); * Blood urea nitrogen (BUN) ≤1.0 × ULN; * Alanine aminotransferase (ALT) ≤1.5 × ULN; * Aspartate aminotransferase (AST) ≤1.5 × ULN; * Alkaline phosphatase (ALP) ≤1.5 × ULN; * Total bilirubin (TBIL) ≤1.5 × ULN; * Negative urine protein; * Normal coagulation function. 8. No contraindications to immunotherapy. 9. No history of hypersensitivity to fluoropyrimidines or platinum-based agents. 10. No prior surgery, chemotherapy, immunotherapy, or other antitumor therapy for gastric or gastroesophageal junction cancer since diagnosis. 11. No previous radiotherapy to the intended irradiation sites. 12. Ability to understand and willingness to sign a written informed consent form.
Exclusion criteria
1. Brain metastases or extensive metastatic disease. 2. Prior treatment with PD-1, PD-L1, TGF-β, CTLA-4 inhibitors, or other investigational immunotherapies. 3. Severe autoimmune diseases, including but not limited to active inflammatory bowel disease (Crohn's disease or ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, or autoimmune vasculitis (e.g., Wegener's granulomatosis). 4. Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis. 5. Conditions associated with an increased risk of gastrointestinal perforation, including active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors. 6. History of another malignancy, except adequately treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or carcinoma in situ of the cervix. 7. Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable cardiac arrhythmia. 8. Any physical examination findings, laboratory abnormalities, or uncontrolled medical conditions that, in the investigator's judgment, may interfere with study outcomes or increase the risk of treatment-related complications. 9. Pregnant or breastfeeding women. 10. Congenital or acquired immunodeficiency, including HIV infection, or a history of organ transplantation or allogeneic hematopoietic stem cell transplantation. 11. Active hepatitis B infection (HBV DNA ≥2,000 IU/mL), active hepatitis C infection, or active tuberculosis. 12. Receipt of any live or other prohibited vaccines within 4 weeks before study treatment. Seasonal inactivated influenza vaccines are permitted, whereas intranasal live attenuated influenza vaccines are not permitted. 13. Concurrent treatment with other immunosuppressive agents, chemotherapy, investigational drugs, or long-term systemic corticosteroids. 14. Psychiatric disorders, substance abuse, or social conditions that may compromise treatment compliance, as determined by the investigator. 15. Known hypersensitivity or contraindication to any study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 12 months | Progression-free survival is defined as the time from initiation of study treatment to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 12 months | Objective response rate is defined as the proportion of participants achieving a complete response or partial response according to RECIST version 1.1. |
| Overall Survival (OS) | up to 3 years | Overall survival is defined as the time from initiation of study treatment to death from any cause. |
| Local Control Rate (LCR) | up to 3 years | Local control rate is defined as the proportion of participants without local disease progression within the irradiated lesions |
| Pathological Complete Response (pCR) | up to 24 months | The proportion of participants with no residual viable tumor cells in the resected specimen following neoadjuvant treatment. |
| Major Pathological Response (MPR) | up to 24 months | The proportion of participants with ≤ 10% residual viable tumor cells in the resected primary tumor. |
| Treatment-Related Adverse Events | up to 24 months | The incidence and severity of treatment-related adverse events will be assessed according to CTCAE version 5.0. |
| Quality of Life | up to 3 years | Quality of life will be assessed using the EORTC QLQ-C30 questionnaire. |
| Exploratory Biomarker Analysis | up to 3 years | Exploratory analyses will quantify biomarker concentrations, count participants presenting biomarker alterations linked to treatment response, and calculate survival rates stratified by biomarker levels. All measured biomarker values, participant counts, and stratified survival rates will be summarized and presented in the outcome measure results data table. |
| R0 Resection Rate | up to 24 months | The proportion of participants who undergo curative-intent surgery and achieve microscopically margin-negative (R0) resection |
Countries
China
Contacts
CONTACTJing Jin, M.D.
PRINCIPAL_INVESTIGATORJing Jin, M.D.
Chinese Academy of Medical Sciences
Outcome results
None listed