Clinical Study of Envafolimab Combined With Fruquintinib and Chemotherapy for Neoadjuvant Treatment of Gastric Cancer

Envafolimab Combined With Fruquintinib and Chemotherapy for Neoadjuvant Treatment of Gastric Cancer: a Single-arm, Open Clinical Study

To observe and evaluate the neoadjuvant treatment of Envafolimab combined with Fruquintinib and chemotherapy for locally advanced gastric/gastroesophageal junction carcinoma

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Envafolimab; Drug: Fruquintinib

Detailed Description

This study observed and evaluated the major pathological response rate (MPR), pathological complete response rate (pCR), pathological response rate (pRR), objective response rate (ORR), R0 removal rate, disease-free survival (DFS) of Envafolimab combined with Fruquintinib and chemotherapy in neoadjuvant therapy for locally advanced gastric/gastroesophageal junctional cancer. Overall survival (OS) and security. The relationship between tumor angiogenesis and lymphangiogenesis and clinical outcome of patients (including but not limited to immunohistochemical detection of CD31, CD3, CD8, etc.) was also explored.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianxin Ye Ye; Phone Number: 13809553280; Email: yejianxinfuyi@126.com

Study Locations

• China
  • Fujian
    • FuZhou, Fujian, China, 350005
      • Recruiting
      • The First Affiliated Hospital of Fujian Medical University
      • Contact: The First Affiliated Hospital FJMU-FAH of Fujian Medical University; Phone Number: +86 0591 87981029; Email: fjydfyjg@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Have fully understood the study and voluntarily signed the informed consent;
2. Aged 18-75 years (including 18 and 75 years);
3. Pathologically confirmed or potentially resectable locally advanced gastric/gastroesophageal junction adenocarcinoma (cT2-T4b, N+M0);
4. If bone metastasis is suspected, a bone scan should be performed. If peritoneal metastasis is suspected, abdominal examination should be performed to rule out distant metastasis.
5. At least 1 measurable lesion according to RECIST v1.1 criteria;
6. United States Eastern Cancer Consortium (ECOG) Physical status score 0-1; BMI≥18;
7. Expected survival ≥12 weeks;

8. The functions of vital organs during the first 14 days of enrollment met the following requirements:

   • Absolute neutrophil count ≥1.5×109/L;
   • Platelet ≥80×109/L;
   • Hemoglobin ≥90g/L;
   • Total bilirubin < 1.5 ULN; ALT and AST < 2.5 ULN (< 5 ULN in patients with liver metastasis);
   • Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr)≥60ml/min;
   • endogenous creatinine clearance > 50ml/min;
9. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age should take effective contraceptive measures during the whole treatment period and 6 months after the treatment period;
10. Good compliance, cooperate with follow-up.

Exclusion Criteria:

1. Known HER2-positive patients;
2. Participated in other drug clinical trials and received at least one drug therapy within 4 weeks prior to enrollment or received other systemic anti-tumor therapy, including chemotherapy, signal transduction inhibitors, immunotherapy, and other investigational drugs within 4 weeks prior to enrollment;
3. Had other malignancies within 5 years prior to admission, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
4. Receive live vaccine within 4 weeks prior to enrollment or possibly during the study period;
5. Had active autoimmune disease or history of autoimmune disease within 4 weeks prior to enrollment;
6. Previously received allogeneic bone marrow transplantation or organ transplantation;
7. The patient has a current disease or condition that affects drug absorption, or the patient cannot take Fruquintinib orally;
8. Subjects who are allergic to the investigational drug or any of its adjuncts;
9. The investigator identified clinically significant electrolyte abnormalities;
10. Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg;
11. Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerative colitis, or active bleeding of unresectable tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers before enrollment;
12. Patients with significant evidence or history of bleeding tendency within 3 months (bleeding >30 mL within 3 months, accompanied by hematemesis, stool, and blood in the stool), hemoptysis (>5 mL of fresh blood within 4 weeks), or thromboembolic events (including stroke events and/or transient ischemic attacks) within 12 months prior to admission;

13. History of severe cardiovascular and cerebrovascular diseases:

    • Cerebrovascular accident (excluding lacunar infarction, minor cerebral ischemia, or transient ischemic attack), myocardial infarction, unstable angina, and poorly controlled arrhythmias (including QTc interval ≥ 450ms for men and 470 ms for women) within 6 months prior to first administration of the study drug (QTc interval Fridericia) Formula calculation);
    • New York Heart Association (NYHA) heart function Grade > II or left ventricular ejection fraction (LVEF) < 50%;
14. Known human immunodeficiency virus (HIV) infection; A known history of clinically significant liver disease, including viral hepatitis [active HBV infection, i.e., positive HBV DNA (>1×104 copies /mL or >2000 IU/ml) must be excluded for a known hepatitis B virus (HBV) carrier; Known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis];

16. Women who are pregnant (positive pregnancy test before medication) or breastfeeding; 17. Two consecutive routine urine tests indicated urine protein ≥2+, and the urine protein volume >1.0g within 24 hours of reexamination; 18. Patients with ascites or pleural effusion with clinical symptoms; 19. CTCAE V5.0 grade 1 or higher toxicity due to any previous anticancer treatment that is not resolved, excluding oxaliplatin induced alopecia, lymphocytopenia, and neurotoxicity ≤ grade 2; 20.Patients considered inappropriate for inclusion in this study.

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: Envafolimab combined with Fruquintinib and chemotherapy	Drug: Envafolimab; 150mg/m2 , IH， d1；Q3W; Drug: Fruquintinib; 5 mg ，po，QD，d1-d14；Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response rate (MPR)	MPR is defined as the proportion of neoadjuvant therapy induced tumor regression with pathologically remaining tumor < 10%	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	pCR is defined as the proportion of patients who do not have residual cancer cells on pathological examination after treatment	up to 12 months
Pathological response rate (pRR)	pRR is defined as the proportion of patients whose pathologic examination after treatment found no cancer cells remaining or whose cancer cells remaining within a pre-specified value range	up to 12 months
Objective response rate (ORR)	ORR is defined as the proportion of patients whose best overall assessment is a complete or partial response.	up to 12 months
Disease-free survival (DFS)	DFS is defined as the time between a patient's enrollment and the onset of tumor recurrence or death from any cause	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 years
Overall survival (OS)	OS is defined as the time until a patient is enrolled and dies from any cause	From date of randomization until the date of death from any cause, assessed up to 10 years
R0 removal rate	R0 resection rate was defined as the proportion of patients with complete resection of the tumor and a negative submicroscopic margin, i.e. no residual tumor	up to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between tumor angiogenesis and lymphangiogenesis and clinical outcomes	Investigate the relationship between tumor angiogenesis, lymphangiogenesis (including but not limited to immunohistochemical detection of CD31, CD3, CD8, etc. expression) and the clinical outcomes (PFS, OS, ORR, etc.) of patients	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: January 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: HMPL-013-E1-GC003

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
• product manufactured in and exported from the U.S.: No