Chemoradiotherapy and SHR-1701 in Patients With Unresectable Gastric Cancer

Official title

Safety and Efficacy of Radiotherapy Combined With Chemotherapy and SHR-1701, a PD-L1(Programmed Death-Ligand 1)/TGF-β(Transforming Growth Factor-beta) Bispecific Antibody, in the Treatment of Unresectable Locally Advanced or Metastatic Gastric Cancer

Overview

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

• Drug COPOX
  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.
• Radiation Radiotherapy
  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.
• Biological SHR-1701
  SHR-1701 (1800 mg) will be administered intravenously on day 1 or each 21-day cycle (Q3W) according to the study protocol.

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: Up to 12 months]

Secondary outcome measures (9)

• Objective Response Rate (ORR) [Time frame: up to 12 months]
• Overall Survival (OS) [Time frame: up to 3 years]
• Local Control Rate (LCR) [Time frame: up to 3 years]
• Pathological Complete Response (pCR) [Time frame: up to 24 months]
• Major Pathological Response (MPR) [Time frame: up to 24 months]
• Treatment-Related Adverse Events [Time frame: up to 24 months]
• Quality of Life [Time frame: up to 3 years]
• Exploratory Biomarker Analysis [Time frame: up to 3 years]
• R0 Resection Rate [Time frame: up to 24 months]

Eligibility criteria

Inclusion criteria

• Male or female participants aged 18 to 75 years.
• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
• Unresectable locally advanced or metastatic gastric cancer, with primary and metastatic lesions amenable to radiotherapy (excluding patients with brain metastases or extensive metastatic disease).
• HER2-negative disease.
• ECOG performance status of 0-1.
• At least one measurable lesion according to RECIST version 1.1.
• 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.
• No contraindications to immunotherapy.
• No history of hypersensitivity to fluoropyrimidines or platinum-based agents.
• No prior surgery, chemotherapy, immunotherapy, or other antitumor therapy for gastric or gastroesophageal junction cancer since diagnosis.
• No previous radiotherapy to the intended irradiation sites.
• Ability to understand and willingness to sign a written informed consent form.

Exclusion criteria

• Brain metastases or extensive metastatic disease.
• Prior treatment with PD-1, PD-L1, TGF-β, CTLA-4 inhibitors, or other investigational immunotherapies.
• 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).
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
• Conditions associated with an increased risk of gastrointestinal perforation, including active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors.
• 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.
• Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable cardiac arrhythmia.
• 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.
• Pregnant or breastfeeding women.
• Congenital or acquired immunodeficiency, including HIV infection, or a history of organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active hepatitis B infection (HBV DNA ≥2,000 IU/mL), active hepatitis C infection, or active tuberculosis.
• 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.
• Concurrent treatment with other immunosuppressive agents, chemotherapy, investigational drugs, or long-term systemic corticosteroids.
• Psychiatric disorders, substance abuse, or social conditions that may compromise treatment compliance, as determined by the investigator.
• Known hypersensitivity or contraindication to any study treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Hospital — Shenzhen
• Shanxi Cancer Hospital — Taiyuan
• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Uni — Beijing

Identifiers

NCT: NCT07689851 · 26/320-6044

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗