Phase II Trial of Neoadjuvant Thymalfasin, PD-1 Inhibitor, and Chemoradiotherapy for cStage III GEJ Adenocarcinoma

NCT07277439 | Recruiting Phase 2

• 1 other identifier: 2025-SR-275
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, randomized controlled, phase II clinical trial. The study aims to enroll 48 patients with resectable, locally advanced gastroesophageal junction adenocarcinoma who have not received any treatment. After obtaining informed consent and meeting the inclusion/exclusion criteria, patients were randomly assigned preoperatively in a 1:2 ratio: Arm A. Radiochemoimmunotherapy group (n=16): 3 cycles of serplulimab combined with modified SOX (mSOX) combined with radiotherapy, as details: Cycle 1: Serplulimab: 300 mg, i.v., D1 Oxaliplatin: 130 mg/m², i.v., D1 S-1 (Tegafur/Gimeracil/Oteracil): Oral administration: 40 mg twice daily for BSA \< 1.25 m²; 50 mg twice daily for BSA 1.25 to \<1.5 m²; 60 mg twice daily for BSA ≥ 1.5 m². Administered from D1 to D14, followed by a rest period from D15 to D21. This cycle lasts 21 days. Cycle 2: Serplulimab: 300 mg, i.v., D1 S-1: Oral administration: 40 mg twice daily from D1 to D14 of the treatment cycle. Radiotherapy: Commences between D2 and D5 after the start of Cycle 2. The clinical target volume (CTV) is defined as the endoscopically marked tumor boundary and adjacent metastatic lymph nodes plus a 5-10 mm margin. The planning target volume (PTV) is generated by adding an additional 5-10 mm margin to the CTV. The planned dose to the PTV is 44 Gy administered in 22 fractions, with 5 fractions per week. This is followed by a 7-day rest interval. This cycle lasts 33 days. Cycle 3: Serplulimab: 300 mg, i.v., D1 Oxaliplatin: 130 mg/m², i.v., D1 Fluorouracil Injection: Administered as a 400 mg/m² intravenous bolus on day 1, followed immediately by a continuous intravenous infusion of 2400-3000 mg/m² over 46 hours. This is followed by a 7-day rest period. This cycle lasts 9 days. Arm B: Immunomodulation group (n=32): 3 cycles of serplulimab combined with mSOX combined with radiotherapy (as described above) and 9 weeks of neoadjuvant thymosin; After neoadjuvant therapy, the efficacy of the therapy and the feasibility of radical D2 resection are assessed through imaging examinations. Efficacy evaluation is performed within 2 weeks of the completion of neoadjuvant therapy, and radical gastrectomy is performed within 4-6 weeks. Postoperative treatment is determined jointly by the clinician and the patient based on actual clinical practice. The primary endpoint is complete pathological response (pCR) rate, defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes. Safety assessment: Safety assessments are performed after each cycle of neoadjuvant therapy and 30 days postoperatively. Event follow-up: Follow-up events are then conducted every 3 months for the first year postoperatively, and every 6 months for 1-2 years, up to 2 years postoperatively.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Complete pathological response (pCR) rate

  Defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes

  from surgery to 1 month after surgery

Secondary Outcomes (6)

• Major Pathological Response (MPR)

  from preoperative to 10 days postoperative

• Tumor Regression Grade (TRG)

  from preoperative to 10 days postoperative

• Objective Response Rate (ORR)

  before surgery

• Disease-free Survival (DFS)

  2 years after surgery

• R0 resection rate

  from preoperative to 10 days postoperative

Study Arms (2)

Immunomodulation group

EXPERIMENTAL

Immunomodulation group (n=32): 3 cycles of serplulimab combined with mSOX combined with radiotherapy and 9 weeks of thymosin-based neoadjuvant therapy;

Other: Immunomodulation

Radiochemoimmunotherapy group

EXPERIMENTAL

Radiochemoimmunotherapy group (n=16): 3 cycles of serplulimab combined with mSOX combined with radiotherapy.

Other: Radiochemoimmunotherapy

Interventions

Radiochemoimmunotherapy OTHER

3 cycles of serplulimab combined with mSOX combined with radiotherapy.

Radiochemoimmunotherapy group

Immunomodulation OTHER

3 cycles of serplulimab combined with mSOX combined with radiotherapy and 9 weeks of thymosin-based neoadjuvant therapy;

Immunomodulation group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent provided.
• Age ≥ 18 years and ≤ 75 years at enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2.
• Life expectancy ≥ 6 months.
• Diagnosis of gastroesophageal junction (GEJ) adenocarcinoma by gastroscopy and histopathology. According to AJCC 8th edition staging, abdominal CT assessment confirms clinical stage cStage III (cT3-4aN1-3M0). For GEJ cancers, only Siewert type III and those Siewert type II cases not requiring combined thoracotomy are eligible.
• Prior to enrollment, a multidisciplinary assessment involving at least one gastrointestinal surgery attending physician and one radiologist confirms cStage III disease, eligibility for R0 resection with curative intent, patient's agreement to undergo radical surgery, and absence of surgical contraindications as judged by the surgeon.
• No prior systemic anti-cancer therapy for the current disease, including surgery, radiotherapy, chemotherapy, immunotherapy, etc.
• Adequate cardiac function to undergo curative-intent resection. Patients with underlying ischemic, valvular, or other significant heart disease should undergo preoperative evaluation by a cardiologist if clinically indicated.
• Adequate organ function, meeting the following laboratory parameters (without supportive measures within specified timeframes):
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (without granulocyte colony-stimulating factor support within 14 days).
• Platelets ≥100 × 10⁹/L (without transfusion within 14 days).
• Hemoglobin \>8 g/dL (without transfusion or erythropoietin use within 14 days).
• Total bilirubin ≤1.5 × upper limit of normal (ULN); OR total bilirubin \>1.5 × ULN but direct bilirubin ≤ ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
• Serum creatinine ≤1.5 × ULN AND calculated creatinine clearance (Cockcroft-Gault formula) ≥60 mL/min.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• History of other malignancies within the past 5 years or concurrent malignancy. Exceptions include cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervical carcinoma in situ, breast carcinoma in situ, Stage I lung cancer, Stage I colorectal cancer, etc.
• Planned or prior organ or bone marrow transplantation.
• Blood transfusion within 2 weeks prior to the first dose, history of bleeding, or any grade 3 or higher bleeding event (per CTCAE v5.0) within 4 weeks prior to screening.
• Coagulation disorders or bleeding tendency (INR \>1.5 times the upper limit of normal \[ULN\] without anticoagulant use). Patients receiving therapeutic anticoagulation with agents such as warfarin, heparin, or analogues. Prophylactic use of low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (≤100 mg daily) is permitted if INR ≤1.5.
• Arterial or venous thromboembolic events within 6 months prior to screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except catheter-related thrombosis secondary to prior chemotherapy deemed resolved by the investigator), and pulmonary embolism.
• Myocardial infarction within 6 months prior to the first dose, or poorly controlled arrhythmias (including QTc interval ≥450 ms for males or ≥470 ms for females, calculated using Fridericia's formula).
• Cardiac insufficiency meeting NYHA Class III-IV criteria, or left ventricular ejection fraction (LVEF) \<50% as measured by echocardiogram.
• Urinalysis showing protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g.
• Clinically symptomatic pleural effusion or ascites requiring intervention.
• Known human immunodeficiency virus (HIV) infection.
• Active pulmonary tuberculosis.
• Non-healing wounds or incompletely healed fractures.
• History or current presence of interstitial lung disease, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function, or other conditions that may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Known active or suspected autoimmune disease. Patients in a stable state of the disease at enrollment (not requiring systemic immunosuppressive therapy) are allowed.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

First Affiliated Hospital of Nanjing Medical Unviersity

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Immunomodulation

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Immune System Phenomena

Central Study Contacts

XU

CONTACT

86-2568306505; liuhongda@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients were randomly assigned preoperatively in a 1:2 ratio: Immunomodulation group (n=32): 3 cycles of serplulimab combined with mSOX combined with radiotherapy and 9 weeks of thymosin-based neoadjuvant therapy; Radiochemoimmunotherapy group (n=16): 3 cycles of serplulimab combined with mSOX combined with radiotherapy. Radiotherapy was initiated 2-5 days after the start of the second cycle of immunochemoimmunotherapy. A 5-10 mm extravasation was made from the endoscopically marked tumor boundary and adjacent metastatic lymph nodes to form a central tumor volume (CTV), and another 5-10 mm extravasation was made to form a partial tumor volume (PTV). The planned PTV treatment time was 44 Gy/22 fractions per minute (F), 5 fractions per week (F/W).

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: December 11, 2025
• Study Start: December 16, 2025
• Primary Completion (Estimated): February 16, 2027
• Study Completion (Estimated): February 16, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-01

Locations

CN (1)