Iparomlimab and Tuvonralimab Injection (QL1706) Combined With DOS as Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction

Phase 2Active Not RecruitingNCT07776639

Yongxu Jia34 enrolled

Overview

This is a single-center, prospective, exploratory clinical study. Eligible patients will be enrolled and receive iapalolimab combined with DOS regimen (docetaxel + oxaliplatin + tegafur-gimeracil-oteracil potassium). The study aims to further explore the efficacy and safety of iapalolimab plus DOS regimen for locally advanced gastric or gastroesophageal junction adenocarcinoma. A total of 34 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma will be enrolled. Each treatment cycle lasts 21 days. After 3-4 cycles, patients who are assessed as operable by investigators will undergo surgical resection, and postoperative pathological results will be evaluated. The primary outcome measure is the pathological complete response rate. Investigators will determine subsequent treatment regimens based on patients' pathological findings and routine clinical practice at the study center. Radiological assessment of tumor response is recommended every 2 cycles.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastroesophageal Junction Adenocarcinoma Gastric Adenocarcinoma

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Aged 18-75 years old, male or female; * Previously untreated, surgically resectable adenocarcinoma of the stomach or gastroesophageal junction; * Clinical stage cT3-4a/N+M0; * ECOG performance status 0-1; * Adequate function of major organs assessed within 7 days before treatment: 1. Hematological indicators (without blood transfusion within 14 days): Hemoglobin (HB) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet (PLT) ≥80×10⁹/L; 2. Biochemical indicators: Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 ml/min; 3. Assessed by Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%); 4. Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN; * Subjects of childbearing potential agree to use effective contraception during the study and for 6 months after the end of study treatment; * Subjects voluntarily participate in this study and sign written informed consent. Exclusion Criteria: * Inclusion Criteria: * Aged 18-75 years old, male or female; * Previously untreated, surgically resectable adenocarcinoma of the stomach or gastroesophageal junction; * Clinical stage cT3-4a/N+M0; * ECOG performance status 0-1; * Adequate function of major organs assessed within 7 days before treatment: 1. Hematological indicators (without blood transfusion within 14 days): Hemoglobin (HB) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet (PLT) ≥80×10⁹/L; 2. Biochemical indicators: Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 ml/min; 3. Assessed by Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%); 4. Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN; * Subjects of childbearing potential agree to use effective contraception during the study and for 6 months after the end of study treatment; * Subjects voluntarily participate in this study and sign written informed consent. Exclusion Criteria: * History of hypersensitivity to any component of QL1706, tegafur-gimeracil-oteracil potassium, oxaliplatin, docetaxel, or any of their excipients; * History of other malignant tumors within the past 5 years or concurrent other malignant tumors, except cured carcinoma in situ of cervix, non-melanoma skin cancer, and superficial bladder tumors; * Patients with distant metastasis or unresectable disease; * Prior receipt of immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4, etc.); * Received any anti-tumor agents within 4 weeks prior to the first study drug administration; * Patients with intestinal obstruction (including incomplete intestinal obstruction) or other gastrointestinal diseases that may lead to gastrointestinal hemorrhage, perforation or obstruction; * Patients with any bleeding event ≥ CTCAE Grade 3, unhealed wounds, ulcers or fractures within 4 weeks before screening; * Concurrent enrollment in another interventional clinical trial, except observational (non-interventional) clinical trials or follow-up phase of interventional trials; * Subjects requiring systemic treatment with corticosteroids (\>10 mg prednisone equivalent daily) or other immunosuppressants within 2 weeks before the first study drug administration; * Received live vaccines within 4 weeks prior to the first study drug administration; * Underwent major surgery or suffered trauma within 4 weeks before the first study drug administration; * Active autoimmune disease or history of autoimmune disease, except vitiligo or childhood asthma/allergy that has resolved and requires no intervention in adulthood; * History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation; * Subjects with inadequately controlled cardiovascular clinical symptoms or diseases; * Severe infection (CTCAE Grade \> 2) occurring within 4 weeks prior to the first study drug administration; * History of interstitial lung disease (except radiation pneumonia without corticosteroid treatment), non-infectious pneumonia, active pulmonary tuberculosis infection; patients with history of active pulmonary tuberculosis infection within 1 year before enrollment, or patients with history of active pulmonary tuberculosis infection more than 1 year ago without standardized treatment; * Pregnant or breastfeeding women; * Other concomitant diseases that, in the investigator's opinion, may seriously endanger the subject's safety or prevent the subject from completing the study.

Outcomes

Primary Outcomes

Pathological Complete Response (pCR) rate

Pathological complete response (pCR) is defined as no residual tumor cells identified in the primary tumor bed and regional lymph nodes after surgical resection, which means complete pathological regression of the tumor.

Time frame: Up to 24 weeks after completion of neoadjuvant therapy and surgical resection

Secondary Outcomes

R0 Resection Rate

R0 resection is defined as complete resection of the tumor lesion. No residual tumor is visible macroscopically, and no tumor cells can be identified microscopically at the resection margins without any residual tumor components, achieving radical surgical effect. The R0 resection rate refers to the proportion of patients who achieve R0 resection.

Time frame: Up to 24 weeks after completion of neoadjuvant therapy and gastrectomy.

Objective Response Rate

Objective Response Rate (ORR) is defined as the proportion of subjects achieving confirmed complete response (CR) plus partial response (PR) as assessed per RECIST version 1.1

Time frame: Up to 12 weeks after completion of neoadjuvant therapy, prior to gastrectomy.

Major Pathological Response (MPR) Rate

Major pathological response (MPR) is defined as ≤10% viable residual tumor cells both in the primary tumor bed and regional lymph nodes after gastrectomy. The MPR rate refers to the proportion of subjects achieving MPR after gastrectomy.

Time frame: Up to 24 weeks after completion of neoadjuvant therapy and gastrectomy.

Disease Control Rate

Disease Control Rate (DCR) is defined as the proportion of subjects achieving confirmed stable disease (SD), partial response (PR), and complete response (CR) as assessed per RECIST version 1.1.

Time frame: Up to 12 weeks after completion of neoadjuvant therapy, prior to gastrectomy

Incidence of Adverse Events

Safety will be evaluated by monitoring the incidence, type, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) according to CTCAE. Assessments include physical examinations, routine laboratory tests, and continuous adverse event collection.

Time frame: From the start of neoadjuvant therapy until 30 days after gastrectomy.

3-year Disease-Free Survival (DFS) Rate

Disease-free survival (DFS) is defined as the time from the date of randomization to the first documented disease recurrence (local recurrence, regional recurrence or distant metastasis) or death from any cause, whichever occurs first. The 3-year DFS rate is the proportion of subjects who remain alive without disease recurrence at 3 years after randomization. Time Frame: From the date of randomization until 3 years after randomization

Time frame: From the date of gastrectomy until 3 years after gastrectomy.