To explore the efficacy of Iparomlimab and Tuvonralimab (QL1706) in combination with SOX chemotherapy versus chemotherapy alone for the neoadjuvant treatment of locally-progressed gastric/gastroesophageal union adenocarcinomas by evaluating the complete pathologic remission rate (pCR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Preoperative QL1706 combined with SOX regimen (4 cycles) → Radical surgery (D2) → Postoperative QL1706 combined with SOX regimen (4 cycles). QL1706 (50mg/2mL) , at a dose of 5mg/kg, the desired volume of drug is withdrawn and slowly infused into an IV bag of 0.9% NaCl, prepared as a diluent with a final concentration of 1-10mg/mL, mixed, and infused intravenously, Q3W, administered on the first day of each cycle.
Preoperative SOX regimen (4 cycles) → radical surgery (D2) → postoperative SOX regimen (4 cycles).
Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.
Postoperative adjuvant therapy is 4 cycles of QL1706+SOX chemotherapy.
Postoperative adjuvant therapy is 4 cycles of SOX chemotherapy.
Shandong Provincial Hospital
Jinan, Shandong, China
RECRUITINGPathological complete response rate (pCR)
Pathological complete response was defined as pT0N0M0
Time frame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.
Major pathological response rate (MPR)
The percentage of surviving tumor cells in the tumor bed after neoadjuvant therapy was ≤10%.
Time frame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.
R0 resection rate
The proportion of patients who completed R0 resection in the total enrolled patients.
Time frame: From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.
Event-free survival (EFS)
From the beginning of the study to the time of the first occurrence of any of the following events, disease progression beyond surgical treatment, local or distant recurrence, death from any cause, etc.
Time frame: From date of neoadjuvant therapy until the date of the first occurrence of the above events, assessed up to 60 months.
Overall survival (OS)
From study inception to patient death from any cause.
Time frame: From the date of diagnosis to the date of death, assessed up to 60 months.
Disease-free survival (DFS)
The time from randomization until disease recurrence or death due to disease progression.
Time frame: From date of neoadjuvant therapy until the date of the disease recurrence or death due to disease progression, assessed up to 60 months.
Surgical safety
The occurrence of postoperative complications including surgical site infection, anastomotic leakage, gastrointestinal bleeding, incisional dehiscence, adhesive bowel obstruction, biliary and celiac fistulae, and unexplained fever (≥37.5°C).
Time frame: From date of neoadjuvant therapy until the date of 30 days post-surgery, assessed up to 17-19 weeks.
Adverse Events
Based on NCI-CTCAE (version 5.0) adverse events (AEs): including type, incidence, grading, severity, duration, and relevance to the study drug
Time frame: From the date of neoadjuvant therapy to the completion of postoperative adjuvant therapy, up to 24 months.
Drug tolerance
The proportion of dose interruptions, dose reductions, and discontinuations due to drug-related toxicity during the study period.
Time frame: From the date of neoadjuvant therapy to the completion of postoperative adjuvant therapy, up to 24-28 weeks.
Prognostic Biomarkers
Biomarkers of interest include PD-L1 expression (assessed by IHC), microsatellite instability (MSI) status (determined by PCR-based testing), tumor mutation burden (TMB) (evaluated using next-generation sequencing), and circulating tumor DNA (ctDNA) levels (quantified via liquid biopsy). The correlation between these biomarkers and treatment efficacy, including progression-free survival (PFS) and overall survival (OS), will be analyzed.
Time frame: From the date of neoadjuvant therapy initiation until the end of postoperative follow-up, up to 24 months.
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