A Study on Immunotherapy Combined With Radiotherapy for Esophagogastric Junction/Gastric Adenocarcinoma

Launched by JIANGSU CANCER INSTITUTE & HOSPITAL · Jun 26, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for certain types of stomach and esophagus cancers, specifically tumors located where the esophagus meets the stomach. The study is testing a combination of immunotherapy—medications that help the body’s immune system fight cancer—and low-dose radiation therapy before surgery. The goal is to see if this combination can help shrink the tumor and improve treatment outcomes for patients whose tumors have specific genetic features (called dMMR or MSI-H) that make them more likely to respond to this kind of therapy.

Adults between 18 and 80 years old who have been recently diagnosed with these cancers and have not yet received any treatment may be eligible to join. To participate, patients must have tumors that can be surgically removed and meet certain health requirements, including good organ function and a reasonably active lifestyle. During the study, participants will receive the immunotherapy drugs combined with low-dose radiation, followed by surgery to remove the tumor. The trial is not yet recruiting, but if eligible, patients can expect close monitoring, regular tests, and follow-up visits to track the treatment’s effects and their overall health. It’s important to note that this study has strict criteria to ensure safety, so not everyone with these cancers will qualify.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Patients voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and agree to follow-up;
• • 2. Patients with esophagogastric junction/gastric adenocarcinoma (Siewert type II/III) confirmed by endoscopic pathology (note: pathologies from other hospitals must be reviewed at our hospital), with dMMR/MSI-H status confirmed by immunohistochemistry or genetic testing;
• • 3. Based on endoscopic, CT, MRI, or PET-CT findings, AJCC 8th edition staging is cT1-2N1-3M0 or T3-T4aN0-3M0;
• • 4. Age between 18 and 80 years, inclusive of both 18 and 80, both genders are eligible;
• • 5. ECOG PS score of 0-1;
• • 6. Presence of measurable and/or non-measurable lesions as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1);
• • 7. No prior systemic anti-tumor treatment (including but not limited to systemic chemotherapy, radiotherapy, molecular targeted therapy, immunotherapy, biologic therapy, local therapy, or investigational drugs);
• 8. The function of major organs must meet the following criteria (no blood components or cell growth factors allowed within 2 weeks before screening):
• • Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• • Platelets ≥ 100 × 10⁹/L;
• • Hemoglobin ≥ 9 g/dL;
• • Serum albumin ≥ 2.8 g/dL;
• • Total bilirubin ≤ 1.5 × ULN, ALT, AST, and/or ALP ≤ 2.5 × ULN;
• • Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula);
• • International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (patients receiving stable-dose anticoagulation therapy such as low-molecular-weight heparin or warfarin with INR within the expected therapeutic range may be enrolled).
• • Females of childbearing potential should undergo a urine or serum pregnancy test within 72 hours prior to the first dose of study drug and must have a negative result. They must also agree to use effective contraception during the study period and for 5 months after the last dose. Male participants whose partners are of childbearing potential must also use effective contraception during the study period and for 7 months after the last dose.
• Exclusion Criteria:
• • 1. History of surgery for gastric or gastroesophageal junction tumor;
• • 2. Immunohistochemistry or genetic testing shows pMMR, MSI-L, or MSS;
• • 3. High risk of gastrointestinal bleeding or perforation;
• • 4. Poor nutritional status, BMI \< 18.5 kg/m², or PG-SGA score ≥ 9;
• • 5. Major surgery or serious trauma within 4 weeks prior to the first use of the study drug;
• • 6. Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• • 7. Previously received or is currently receiving any of the following treatments: anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
• • 8. Received any investigational drug within 4 weeks prior to the first use of the study drug;
• • 9. Requires systemic corticosteroids (more than 10 mg/day prednisone equivalent) or other immunosuppressive agents within 2 weeks prior to the first use of the study drug, except for local inflammation of the esophagus/stomach and corticosteroid use for allergy prevention or nausea/vomiting control. Special circumstances require communication with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal corticosteroid replacement at doses \>10 mg/day prednisone equivalent are allowed;
• • 10. Has received an anticancer vaccine or received a live vaccine within 4 weeks prior to the first administration of the study drug;
• • 11. Has any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism), except for vitiligo or resolved childhood asthma/allergy that does not require intervention in adulthood. Patients on stable-dose thyroid hormone replacement for autoimmune hypothyroidism and those on stable-dose insulin for type I diabetes mellitus may be included;
• • 12. History of immunodeficiency, including HIV-positive status, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
• • 13. Any condition requiring systemic corticosteroid treatment (higher than 10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days before treatment initiation (except for the following situations: locally applied, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption; short-term (≤7 days) prophylactic use of corticosteroids (e.g., for contrast agent allergy prevention) or for non-autoimmune conditions (e.g., delayed hypersensitivity reactions due to allergen exposure));
• • 14. Presence of uncontrolled cardiac symptoms or diseases such as (1) NYHA class II or higher heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, or (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• • 15. Severe infection (CTCAE \> Grade 2) within 4 weeks prior to the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; baseline chest imaging suggests active pulmonary infection; signs or symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks prior to enrollment, except for prophylactic antibiotic use;
• • 16. History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute pulmonary diseases;
• • 17. Evidence of active tuberculosis infection by medical history or CT findings, or history of active tuberculosis within 1 year prior to enrollment, or history of active tuberculosis more than 1 year ago without proper treatment;
• • 18. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or hepatitis C (anti-HCV positive and HCV-RNA above the lower limit of detection of the assay method);
• • 19. Laboratory abnormalities in sodium, potassium, or calcium levels greater than Grade 1 within 2 weeks prior to enrollment, which cannot be corrected after treatment;
• • 20. Known allergy, hypersensitivity, or contraindication to macromolecular protein preparations, PD-1 components, paclitaxel, capecitabine, or any excipients in their formulations;
• • 21. History of any other malignancy, except for low-risk malignancies with low metastasis and mortality risk (5-year survival rate \>90%), such as adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ;
• • 22. Pregnant or lactating women; fertile subjects unwilling or unable to take effective contraceptive measures;
• • 23. The investigator determines that the subject has other factors likely to result in premature termination of the study, such as other serious illnesses (including mental illness) requiring concurrent treatment, recent serious illnesses (e.g., myocardial infarction, cerebrovascular accident) with high recurrence risk, severely abnormal laboratory values, family or social factors that may affect the subject's safety or data collection from the trial.