NCT07053332Not yet recruitingPhase 2
A Single-arm, Prospective Phase II Clinical Study of Neoadjuvant PD-1/CTLA-4 Combination Antibody With Low-dose Radiotherapy in Resectable dMMR/MSI-H Esophagogastric Junction/Gastric Adenocarcinoma.
Jiangsu Cancer Institute & Hospital0 sites20 target enrollmentStarted: July 1, 2025Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 20
- Primary Endpoint
- Pathological complete response rate (pCR)
Study Overview
Brief Summary
A single-arm, prospective phase II clinical study of neoadjuvant PD-1/CTLA-4 combination antibody with low-dose radiotherapy in resectable dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma.
Detailed Description
This study is a prospective, single-center, single-arm Phase II clinical trial. Participants will be patients with resectable locally advanced dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma staged as cT1-2N1-3M0 or T3-T4aN0-3M0 according to the AJCC/UICC staging system. The objective of this study is to evaluate the safety and efficacy of PD-1/CTLA-4 combination antibody therapy combined with low-dose radiotherapy in patients with locally advanced resectable dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma.
Eligible participants who meet the inclusion criteria will be enrolled in the study.
Primary endpoint: Pathological complete response rate (pCR), defined as pT0N0M0，Safety: Treatment-related adverse reactions of grade 3 or above according to CTCAE 5.0 will be recorded from the start of treatment until 30 days after surgery..
Secondary endpoints:
Treatment feasibility: the proportion of patients who complete neoadjuvant therapy and undergo surgery within 3-5 weeks after treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and agree to follow-up;
- •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;
- •Based on endoscopic, CT, MRI, or PET-CT findings, AJCC 8th edition staging is cT1-2N1-3M0 or T3-T4aN0-3M0;
- •Age between 18 and 80 years, inclusive of both 18 and 80, both genders are eligible;
- •ECOG PS score of 0-1;
- •Presence of measurable and/or non-measurable lesions as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1);
- •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);
- •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
- •History of surgery for gastric or gastroesophageal junction tumor;
- •Immunohistochemistry or genetic testing shows pMMR, MSI-L, or MSS;
- •High risk of gastrointestinal bleeding or perforation;
- •Poor nutritional status, BMI < 18.5 kg/m², or PG-SGA score ≥ 9;
- •Major surgery or serious trauma within 4 weeks prior to the first use of the study drug;
- •Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Previously received or is currently receiving any of the following treatments: anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
- •Received any investigational drug within 4 weeks prior to the first use of the study drug;
- •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;
- •Has received an anticancer vaccine or received a live vaccine within 4 weeks prior to the first administration of the study drug;
- •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;
- •History of immunodeficiency, including HIV-positive status, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
- •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));
- •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;
- •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;
- •History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute pulmonary diseases;
- •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;
- •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);
- •Laboratory abnormalities in sodium, potassium, or calcium levels greater than Grade 1 within 2 weeks prior to enrollment, which cannot be corrected after treatment;
- •Known allergy, hypersensitivity, or contraindication to macromolecular protein preparations, PD-1 components, paclitaxel, capecitabine, or any excipients in their formulations;
- •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;
- •Pregnant or lactating women; fertile subjects unwilling or unable to take effective contraceptive measures;
- •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.
Arms & Interventions
PD-1/CTLA-4 combination antibody with low-dose radiotherapy
Experimental
Intervention: PD-1/CTLA-4 combination antibody with low-dose radiotherapy (Drug)
Outcomes
Primary Outcomes
Pathological complete response rate (pCR)
Time Frame: Assessed average of 1 month after surgery
Pathological complete response is defined as pT0N0M0.
Safety
Time Frame: From the start of treatment until 30 days after surgery
Treatment-related adverse reactions of grade 3 or above according to CTCAE 5.0 will be recorded from the start of treatment until 30 days after surgery.
Secondary Outcomes
- Overall survival (Overall Survival, OS)(From the time of enrollment, until the disease relapses or metastasizes，assessed up to 5 years follow-up.)
- Major pathological response rate (Major pathological response, MPR)(Assessed average of 1 month after surgery)
- R0 resection rate (Complete Resection With no Tumor Within 1 mm of the Resection Margins (R0) Rate)(Assessed average of 1 month after surgery)
- Post-operative complications(Assessed average of 1 month after surgery)
- Time to relapse (Time to Relapse, TTR)(From the time of enrollment, until the disease relapses or metastasizes，assessed up to 5 years follow-up.)
- Progression-free survival (Progression-free survival, PFS)(From the time of enrollment, until the disease relapses or metastasizes，assessed up to 5 years follow-up.)
Investigators
Chao Yue
Chief Physician
Jiangsu Cancer Institute & Hospital
Similar Trials
Recruiting
Phase 2
The Combination of Immunotherapy and Neoadjuvant Short-course Radiotherapy in Early Rectal CancerEarly Low Rectal CancerNCT05555888Fudan University34
Unknown
Phase 1
CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells for EGFR Positive Advanced Solid TumorAdvanced Solid TumorNCT03182816Shanghai Cell Therapy Research Institute40
Unknown
Phase 1
CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for MUC1 Positive Advanced Solid TumorAdvanced Solid TumorNCT03179007Shanghai Cell Therapy Research Institute40
Not yet recruiting
Phase 2
Cadonilimab Plus Nab -Paclitaxel for Patients With Recurrent, or Metastatic Cervical Cancer Resistant to Immune Checkpoint InhibitorsCervical NeoplasmsUterine Cervical NeoplasmsCancer of CervixUterine Cervical CancerCancer of the Uterine CervixCervical CancerNCT05824494Women's Hospital School Of Medicine Zhejiang University58
Recruiting
Phase 2
Clinical Study of Neoadjuvant PD-1 Antibody (Toripalimab) Plus Chemotherapy for Locally Advanced Thymic Epithelial TumorThymic Epithelial TumorNCT04667793Shanghai Pulmonary Hospital, Shanghai, China15