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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
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.
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.
SHR-1701 (1800 mg) will be administered intravenously on day 1 or each 21-day cycle (Q3W) according to the study protocol.
Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGShanxi Cancer Hospital
Taiyuan, Shanxi, China
RECRUITINGNational Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, China
RECRUITINGProgression-Free Survival (PFS)
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.
Time frame: Up to 12 months
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of participants achieving a complete response or partial response according to RECIST version 1.1.
Time frame: up to 12 months
Overall Survival (OS)
Overall survival is defined as the time from initiation of study treatment to death from any cause.
Time frame: up to 3 years
Local Control Rate (LCR)
Local control rate is defined as the proportion of participants without local disease progression within the irradiated lesions
Time frame: up to 3 years
Pathological Complete Response (pCR)
The proportion of participants with no residual viable tumor cells in the resected specimen following neoadjuvant treatment.
Time frame: up to 24 months
Major Pathological Response (MPR)
The proportion of participants with ≤ 10% residual viable tumor cells in the resected primary tumor.
Time frame: up to 24 months
Treatment-Related Adverse Events
The incidence and severity of treatment-related adverse events will be assessed according to CTCAE version 5.0.
Time frame: up to 24 months
Quality of Life
Quality of life will be assessed using the EORTC QLQ-C30 questionnaire.
Time frame: up to 3 years
Exploratory Biomarker Analysis
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.
Time frame: up to 3 years
R0 Resection Rate
The proportion of participants who undergo curative-intent surgery and achieve microscopically margin-negative (R0) resection
Time frame: up to 24 months
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