Neoadjuvant Adebrelimab + DOS in Locally Advanced Resectable Gastric Cancer

Phase II Study of Neoadjuvant Adebrelimab, Docetaxel, Oxaliplatin, and S-1 in Patients With Resectable Advanced Gastric Cancer

To evaluate the efficacy and safety of adebrelimab combined DOS in neoadjuvant treatment of locally advanced resectable gastric cancer.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Adebrelimab combined with DOS

Detailed Description

This prospective, single-center, single-arm clinical trial aims to enroll 42 treatment-naïve patients diagnosed with locally advanced gastric adenocarcinoma who are deemed operable. Following informed consent, patients will undergo screening to confirm eligibility. Subsequently, eligible participants will receive the standard dosage of Adebrelimab in combination with the DOS regimen for three cycles as neoadjuvant therapy prior to surgery. Within 3-6 weeks after completing the third cycle, preoperative imaging will be conducted to assess the efficacy of the novel neoadjuvant treatment and feasibility of achieving radical D2 resection. Patients will then undergo radical surgical resection for gastric cancer, with pathological complete response (pCR) being observed.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nan Wang, Dr; Phone Number: 15719286297; Email: wangnandoc@163.com

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710038
      • Recruiting
      • Tangdu Hospital Affiliated to the Fourth Military Medical University
      • Contact: Nan Wang, Dr; Phone Number: 15719286297; Email: wangnandoc@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Participants will be recruited voluntarily and will provide informed consent before enrollment. They are expected to demonstrate good compliance and willingness to adhere to the study protocol, including attending follow-up visits as required.
2. Inclusion criteria for participant eligibility are as follows:

1）Age between 18 and 75 years, with no gender restrictions. 2）Histopathological confirmation of locally advanced gastric or gastroesophageal junction adenocarcinoma obtained through gastric endoscopic biopsy.

3）Clinical staging consistent with T2-3N+M0 or T4aNanyM0, confirmed by imaging (CT/MRI) and endoscopic ultrasound.

4）Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 5）Expected survival of at least 12 weeks. 3.Prior to treatment initiation, participants must meet the following criteria related to vital organ function within the preceding 7 days:

1. Hematological parameters: Hemoglobin (Hb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, Platelets (PLT) ≥ 80 × 10^9/L (no recent blood transfusions within 14 days).
2. Biochemical parameters: 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 rate (CCr) ≥ 60 ml/min.
3. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).

4.Female participants of childbearing potential must agree to use effective contraception during the study and for 6 months after the end of the study period. They must provide negative serum or urine pregnancy tests within 7 days before enrollment and must not be lactating. Male participants must also agree to use effective contraception during the study and for 6 months following its conclusion.

5.All participants must provide voluntary informed consent before participation in the study.

Exclusion Criteria:

1. History of malignancies within the past 5 years, excluding cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors.
2. Patients with tumors invading adjacent organs (e.g., aorta or trachea), posing a high risk of bleeding or fistula formation.
3. Subjects requiring systemic treatment with corticosteroids (>10 mg prednisone or equivalent daily) or other immunosuppressive agents within 14 days prior to study treatment initiation, except for those with no active autoimmune disease who may receive inhaled or topical corticosteroids at doses equivalent to >10 mg prednisone daily or adrenal replacement steroid doses.
4. Patients with significant malnutrition requiring intravenous nutrition or continuous infusion therapy requiring hospitalization. Patients with well-controlled nutrition for ≥28 days before randomization may be included.
5. Participants receiving live vaccines/attenuated vaccines within 30 days after the first treatment.
6. Unresolved toxicities of grade ≥4 as per CTCAE 4.02 due to previous treatments, excluding alopecia and ≤grade 2 neuropathy caused by oxaliplatin.
7. Allergic reactions or contraindications to any study drug components.
8. Patients with severe and/or uncontrolled diseases, including hypertension, myocardial ischemia or infarction, arrhythmias, congestive heart failure, severe or uncontrolled diseases or active infections, renal failure, immunodeficiency diseases, poorly controlled blood glucose, seizures, history of interstitial lung disease, pulmonary fibrosis, or any condition interfering with the detection and management of suspected drug-related toxicities.
9. Patients with current gastrointestinal diseases such as intestinal obstruction or those at risk of gastrointestinal bleeding, perforation, or obstruction.
10. Patients who have undergone surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to enrollment.
11. Patients with any bleeding events of grade ≥3 per CTCAE within 4 weeks before enrollment, or those with unhealed wounds, ulcers, or fractures.
12. Participants with thrombotic events (arterial or venous) within 3 months, such as cerebrovascular accidents, deep vein thrombosis, or pulmonary embolism.
13. Subjects planning to undergo or who have previously undergone allogeneic organ or bone marrow transplantation, including liver transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adebrelimab combined with DOS; After signing the informed consent, they are screened to meet the inclusion criteria. After receiving the standard dose of adebrelimab combined with DOS regimen for 3 courses of treatment before surgery, and within 3-6 weeks after the completion of the third administration, preoperative imaging examination is used to evaluate the efficacy of new adjuvant treatment and the possibility of radical D2 resection, The patient underwent radical surgical treatment for gastric cancer and observed pCR.

Drug: Adebrelimab combined with DOS; After signing the informed consent, they are screened to meet the inclusion criteria. After receiving the standard dose of adebrelimab combined with DOS regimen for 3 courses of treatment before surgery, and within 3-6 weeks after the completion of the third administration, preoperative imaging examination is used to evaluate the efficacy of new adjuvant treatment and the possibility of radical D2 resection, The patient underwent radical surgical treatment for gastric cancer and observed pCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate（pCR）	Pathological complete response rate according to Becker standard	7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR)	MPR is defined as less than 10% residual viable tumor after neoadjuvant therapy.	7 days after surgery
Disease-free survival（DFS）	The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer	Long term follow-up will continue until the death of the subject or the end of the study, at least three years
R0 resection rate	Proportion of R0 level surgery performed.	postoperative 6 hours
Overall Survival（OS）	Overall survival (OS) refers to the time that researchers evaluate from recording the first chemotherapy to death (of any cause).	Long term follow-up will continue until the death of the subject or the end of the study, at least three years
Objective response rate（ORR）	Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments, is defined as the number (%) of patients with response of Complete Response or Partial Response.	7 days before surgery
Event-free survival（EFS）	The length of time after primary treatment for a cancer ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay.	Preoperative progression, postoperative recurrence, and death from any cause
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse reactions to chemotherapy and immunotherapy were graded according to the NCI-CTCAE4.0 grading criteria	Long term follow-up will continue until the death of the subject or the end of the study, at least three years

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Collaborators: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2024
• Primary Completion (Estimated): May 20, 2025
• Study Completion (Estimated): April 26, 2026

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Gastric Cancer; Resectable; Neoadjuvant; ICIs
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: 202404-05

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