Adebrelimab Combined With SOX Regimen in Preoperative Neoadjuvant Transformation Therapy for Locally Advanced Gastric Adenocarcinoma

The Safety and Efficacy of Adebrelimab Combined With SOX Regimen in Preoperative Neoadjuvant Therapy for Locally Advanced Gastric Adenocarcinoma Patients (ASOG-01)

Abstract Objective: Adebrelimab is a PD-L1 inhibitor. The aim of this trial is to evaluate the safety and efficacy of adebrelimab combined with SOX regimen for preoperative neoadjuvant therapy in locally advanced gastric adenocarcinoma.

Methods and analysis: This study is a prospective single-center, two-arm, double-blind and randomized controlled clinical trial designed to include 110 patients with locally advanced gastric adenocarcinoma who will be randomly assigned into two groups: experimental group (adebrelimab combined with SOX regimen) (n=55) and control group (SOX regimen) (n=55). The main efficacy indicators are pathological complete response rate (pCR). The secondary efficacy indicators are R0 resection rate, safety indicators (including surgical and drug treatment safety indicators). disease-free survival (DFS) and overall survival (OS).

Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232357-F-1).

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Adebrelimab combined with SOX regimen; Drug: Placebo combined with SOX (S-1/oxaliplatin) regimen

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jianjun Yang, professor; Phone Number: 86+29-84771531; Email: yangjj@fmmu.edu.cn
• Study Contact Backup: Name: Juan Wang, doctor; Phone Number: 86+29-84771532; Email: wangjuan861016@126.com

Study Locations

• China
  • Xi'an, China
    • Recruiting
    • The First Affiliated Hospital of the Air Force Medical University
    • Contact: Jianjun Yang; Phone Number: 029-84771532; Email: yangjj@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

The inclusion criteria is as follows:

Patients are able to and willing to provide written informed consent to participate in the study.

Patients are aged 18-75 years old with an Eastern Cooperative Oncology Group (ECOG) score: 0-1 points and expected survival time ≥ 12 weeks.

Patients are diagnosed with gastric adenocarcinoma by pathological examination and the clinical stage should be clinical stage III (T3-4a/N+M0, T3-4a/N-M0), the tumor of the patients with adenocarcinoma of the gastroesophageal junction should be not involve the dentate line.

Functions of the major organs and bone marrow meet the following criteria within 7 days before treatment: hemoglobin ≥ 90g/L, absolute neutrophil count ≥ 1.5 × 109/L, platelet (PLT) ≥ 80× 109/L, without blood transfusion within 14 days, total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN, serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 60mL/min.

Doppler ultrasound: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%).

Have not received anti-tumor treatment (such as surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy).

The exclusion criteria is as follows:

Other malignant tumors that have occurred or are currently present within 5 years, excluding cured cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumors.

Patients who require systemic treatment with corticosteroids (>10mg prednisone equivalent dose per day) or other immunosuppressive drugs within 14 days before the start of treatment.

Patients with significant malnutrition. Patients receiving live/attenuated vaccines during treatment. Patients with any severe and/or uncontrollable diseases, including hypertension who cannot be well controlled with antihypertensive medication (systolic blood pressure ≥ 150mm Hg, diastolic blood pressure ≥ 100mm Hg); grade I or above myocardial ischemia or infarction, arrhythmia (including QTc ≥ 480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); severe or uncontrolled active infections (≥ CTCAE2 level infection); renal failure requires hemodialysis or peritoneal dialysis; patients with a history of immune deficiency, including those who are HIV positive or suffer from other acquired or congenital immune deficiency diseases; poor blood glucose control in diabetes patients (fasting blood glucose (FBG)>10mmol/L); patients with epileptic seizures who require treatment; patients with previous and current history of interstitial lung disease, pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc., may interfere with the detection and management of suspected drug-related pulmonary toxicity; patients with gastrointestinal bleeding, perforation, or obstruction.

Patients with any bleeding event ≥ CTCAE3 level within the first 4 weeks of enrollment, as well as patients with unhealed wounds, ulcers, or fractures.

Patients who have experienced arterial/venous thrombosis events within 3 months, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism.

Patients who are preparing to undergo or have previously received allogeneic organ or bone marrow transplantation.

According to the judgment of the researchers, patients with other accompanying diseases that seriously endanger patient safety or affect the completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adebrelimab combined with SOX regimen; Adebrelimab combined with SOX regimen preoperatively used 3 cycles(stop adebrelimab and S-1/oxaliplatin after 3 cycles and evaluate tumor staging)→ radical surgery (D2) →Postoperative selection of continued medication or cessation of treatment will base on the patient's pathological reports. Surgery should be performed within 3-6 weeks after 3 cycles of preoperative neoadjuvant therapy.	Drug: Adebrelimab combined with SOX regimen; Adebrelimab combined with SOX regimen preoperatively used 3 cycles(stop adebrelimab and S-1/oxaliplatin after 3 cycles and evaluate tumor staging)→ radical surgery (D2) →Postoperative selection of continued medication or cessation of treatment will base on the patient's pathological reports. Surgery should be performed within 3-6 weeks after 3 cycles of preoperative neoadjuvant therapy.
Active Comparator: Placebo combined with SOX (S-1/oxaliplatin) regimen; Placebo combined with SOX (S-1/oxaliplatin) regimen preoperatively used 3 cycles(stop placebo and S-1/oxaliplatin after 3 cycles and evaluate tumor staging)→ radical surgery (D2) →Postoperative selection of continued medication or cessation of treatment will base on the patient's pathological reports. Surgery should be performed within 3-6 weeks after 3 cycles of preoperative neoadjuvant therapy.	Drug: Placebo combined with SOX (S-1/oxaliplatin) regimen; Placebo combined with SOX (S-1/oxaliplatin) regimen preoperatively used 3 cycles (stop placebo and S-1/oxaliplatin after 3 cycles and evaluate tumor staging) → radical surgery (D2) →Postoperative selection of continued medication or cessation of treatment will base on the patient's pathological reports. Surgery should be performed within 3-6 weeks after 3 cycles of preoperative neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pathological complete response rate (pCR)	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 resection rate	48 months
OS	overall survival	48 months
DFS	disease-free survival	48 months
AE	the incidence of adverse events (AE)	48 months

Collaborators and Investigators

• Sponsor: Yang Jianjun, PhD

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 19, 2023
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled clinical trial; Adebrelimab; SOX regimen; Preoperative neoadjuvant transformation therapy; Locally advanced gastric adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: ASOG-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No