This is an open-label, prospective, interventional study designed to enroll 34 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma, aiming to evaluate and observe the efficacy and safety of QL1706 in combination with DOS for the treatment of locally advanced gastric or gastroesophageal junction adenocarcinoma. Enrolled patients will receive iparomlimab and tuvonralimab in combination with the DOS regimen (docetaxel + oxaliplatin + S-1) administered in 21-day treatment cycles. Subjects who complete 3-4 cycles of treatment and are deemed suitable for surgery will undergo gastrectomy, with the specific interval between neoadjuvant therapy and surgery determined by the investigator based on actual clinical circumstances. Following surgery, clinicians will administer postoperative treatment according to the postoperative pathological assessment results and the clinical practice treatment principles of the study center. The primary endpoint is the pathological complete response rate assessed by postoperative pathological evaluation.
Aged 18 to 75 years; male or female.
Previously untreated, resectable adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
Clinical stage cT3-4a/N+ M0.
ECOG performance status 0-1.
Known history of hypersensitivity or allergy to QL1706 or its excipients, tegafur/gimeracil/oteracil (S-1), oxaliplatin, docetaxel, or any of their excipients.
History of another malignancy within 5 years prior to screening or concurrent malignancy, except for curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors.
Patients with distant metastasis and/or unresectable disease;
Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents.
Single group
Iparomlimab and Tuvonralimab Injection (QL1706)
Drug5 mg/kg, intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
Docetaxel
Drug40 mg/m², intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
Oxaliplatin
Drug100 mg/m², intravenous infusion, administered once every 21 days (D1), for 3-4 cycles.
Tegafur-Gimeracil-Oteracil
Drug40 mg/m², oral, twice daily (BID), D1-14, every 21 days per cycle, for 3-4 cycles.
Gastrectomy
Procedure/SurgerySubjects who complete 3-4 cycles of neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy. The specific interval between neoadjuvant therapy and surgery will be determined by the investigator based on actual clinical circumstances.
Pathological Complete Response Rate (pCR Rate)
Defined as the proportion of patients with no residual tumor cells in the resected tumor tissue and regional lymph nodes upon pathological evaluation.
R0 Resection Rate
The proportion of patients with microscopically margin-negative resection, with no residual tumor cells either macroscopically or microscopically, and complete resection of the lesion.
Major Pathological Response Rate (MPR Rate)
Defined as the proportion of patients with ≤10% residual viable tumor cells in the postoperative pathological specimen.
Objective Response Rate (ORR)
The proportion of patients achieving complete response (CR) or partial response (PR) as assessed by RECIST version 1.1 criteria.
Disease Control Rate (DCR)
The proportion of patients achieving CR, PR, or stable disease (SD) among evaluable patients as assessed by RECIST version 1.1 criteria.
Peripheral blood ctDNA Biomarker
Serial peripheral blood samples are collected at baseline and during neoadjuvant treatment. Circulating tumor DNA (ctDNA) molecular profiles are detected by next-generation sequencing. The exploratory analysis aims to evaluate the correlation between dynamic ctDNA alterations and treatment efficacy and safety outcomes.
Peripheral blood multi-omics biomarker levels
Serial peripheral blood samples are collected at baseline and during neoadjuvant treatment. Genomic, transcriptomic, and proteomic multi-omics profiles in peripheral blood are detected using a multi-omics sequencing platform. Exploratory analyses are performed to explore the association between peripheral blood multi-omics molecular features and treatment efficacy and safety.
Tumor tissue multi-omics and tumor microenvironment immune signatures
Tumor specimens including fresh tissues and formalin-fixed paraffin-embedded (FFPE) sections are collected at baseline (pre-treatment biopsy) and immediately after radical gastrectomy. Baseline and post-operative tumor tissues are subjected to genomic, transcriptomic, and proteomic multi-omics sequencing to characterize tumor biomarkers and tumor microenvironment immune molecular features. All tissue collections do not interfere with routine clinical pathological diagnosis, and are performed with written informed consent. Exploratory analyses will investigate the associations between tissue molecular signatures and treatment efficacy and safety outcomes.
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The First Affiliated Hospital of Zhengzhou University
Lead sponsor
Qilu Pharmaceutical Co., Ltd.
Collaborator
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