Perioperative Ivonescimab Plus S-1 and Oxaliplatin (SOX) for Locally Advanced Gastric or GEJ Adenocarcinoma

Phase 2Not Yet RecruitingNCT07374250

Sichuan University154 enrolled

Overview

The purpose of this clinical trial is to evaluate whether perioperative ivonescimab in combination with S-1 and oxaliplatin (SOX) is effective in treating locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study will also assess the safety profile of this treatment regimen. Primary Objective: To determine whether perioperative ivonescimab plus SOX improves the pathological complete response (pCR) rate compared with SOX alone in patients with locally advanced gastric or GEJ adenocarcinoma. Study Design: Participants will be randomly assigned to receive either ivonescimab plus SOX or SOX alone to evaluate the potential added benefit of ivonescimab in this setting. Participation Details: Participants will receive the assigned treatment (ivonescimab plus SOX or SOX alone) every 21 days for approximately 4 months. They will visit the clinic once every 3 weeks for evaluations, laboratory tests, and monitoring. Participants will be asked to keep a daily diary to record any symptoms or side effects experienced during the study.

To evaluate the efficacy and safety of ivonescimab in combination with S-1 and oxaliplatin (SOX) for the treatment of locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant (perioperative) setting, with the goal of improving the pathological complete response (pCR) rate.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

154

Conditions

Gastric Cancer

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 18-75 years. 2. Histologically confirmed gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinically staged as T3-4a N+ M0 by computed tomography (CT) or magnetic resonance imaging (MRI). 5. Considered eligible for curative resection. 6. No prior antitumor therapy for the current disease. 7. Adequate organ function, including hepatic, renal, and bone marrow function, as per prespecified laboratory criteria. 8. Expected survival of ≥6 months. Exclusion Criteria: 1. Known mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumor. 2. Uncontrolled hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite optimized antihypertensive therapy, or hypertension complicated by acute events (e.g., hypertensive crisis, hypertensive encephalopathy) that cannot be stably controlled. 3. Tumor lesions with a bleeding tendency, including but not limited to: active ulcerative tumor lesions, hematemesis within 2 months prior to informed consent, high risk of major gastrointestinal bleeding as determined by the investigator. 4. History of thromboembolic or arterial/venous vascular events within 6 months prior to enrollment, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism. 5. Gastrointestinal perforation or gastrointestinal obstruction within 6 months prior to enrollment.

Outcomes

Primary Outcomes

Total pathological complete response (pCR; ypT0) assessed by investigators, defined as the complete absence of tumor cells in the primary tumor on pathological examination.

Time frame: Perioperative

Secondary Outcomes

Event-free survival (EFS)

Event-free survival (EFS), defined as the time from randomization to the first occurrence of relapse, metastasis, or death from any cause;

Time frame: Through study completion,an average of 2 years

major pathologic response

defined as ≤10% residual viable tumor cells in the resected primary tumor specimen after neoadjuvant therapy;

Time frame: Perioperative

R0 resection

defined as microscopically margin-negative resection

Time frame: Perioperative

overall survival (OS)

defined as the time from randomization to death from any cause;

Time frame: Through study completion,an average of 2 years

disease-free survival (DFS)

defined as the time from the post-surgery baseline scan to the first occurrence of relapse, metastasis, or death from any cause

Time frame: Through study completion,an average of 2 years

safety

Treatment-related adverse events (TRAEs) with potential immunologic etiology were categorized and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0)

Time frame: Through study completion,an average of 2 years

surgery-related complications

were graded according to the Clavien-Dindo classification;

Time frame: Through study completion,an average of 2 years

An exploratory endpoint

was the evaluation of potential predictive biomarkers associated with treatment response

Time frame: Through study completion,an average of 2 years

Quality of life

Quality of life was assessed using the EORTC QLQ-STO22 and EORTC QLQ-C30 questionnaires, administered at three time points: within one week before initiation of neoadjuvant therapy, within one week before the fourth neoadjuvant therapy cycle, and at 30 days postoperatively (±3 days)

Time frame: Perioperative

Perioperative Ivonescimab Plus S-1 and Oxaliplatin (SOX) for Locally Advanced Gastric or GEJ Adenocarcinoma

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts