Combining Fruquintinib with PD-1 inhibitors for advanced gastric cancer treatment

Efficacy and Safety of Fruquintinib in Combination With PD-1 Inhibitors as First-line Maintenance Therapy for Advanced HER-2 Negative Gastric Cancer: a Single-arm, Prospective, Exploratory Clinical Study

This study is testing if combining Fruquintinib with PD-1 inhibitors can help people with advanced HER-2 negative gastric cancer feel better after their initial treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First People's Hospital of Changzhou (Academic / other)
• Drugs / interventions: nivolumab, sindilizumab, tirelizumab, bevacizumab, apatinib, anlotinib, lenvatinib, chemotherapy, immunotherapy, Fruquintinib
• Locations: 1 site (Changzhou, Jiangsu)
• Trial ID: NCT05721651 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of Fruquintinib, a VEGFR inhibitor, in combination with PD-1 inhibitors as a first-line maintenance therapy for patients with advanced HER-2 negative gastric cancer. The study aims to determine if this combination can provide better outcomes compared to existing treatments. Participants will be closely monitored for their response to the treatment and any potential side effects. The trial is designed as a single-arm, prospective, exploratory study, focusing on patients who have previously received chemotherapy and PD-1 inhibitors.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with advanced HER-2 negative gastric adenocarcinoma who have shown no disease progression after first-line treatment.

Not a fit: Patients with HER-2 positive gastric cancer or those who have not received prior PD-1 inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with advanced HER-2 negative gastric cancer.

How similar studies have performed: Previous studies have shown promising results with combinations of immunotherapy and antiangiogenic agents, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 years old, regardless of gender, volunteer to participate in the trial and sign informed consent；
2. Advanced gastric adenocarcinoma confirmed by pathology (including gastroesophageal junction adenocarcinoma) with extragastric measurable lesions (RECIST 1.1 criteria)；
3. Advanced HER-2-negative gastric cancer patients who received first-line PD-1 inhibitors (nivolumab/sindilizumab/tirelizumab) combined with standard chemotherapy and were assessed as non-PD according to RECIST 1.1 criteria；Chemotherapy regimen: SOX/FOLFOX/CAPEOX or fluorouracil combined with purple shirt；Patients receiving single-agent chemotherapy were allowed to enroll；Chemotherapy regimens are used for 4-8 cycles；
4. ECOG score: 0-1；
5. Expect to survive for at least 3 months；
6. Major organ function within 7 days before treatment meets the following criteria: (1) hemoglobin (HB) ≥90 g/L； (2) Absolute neutrophil ANC ≥1.5×109/L； (3) Platelet (PLT) ≥100×109/L；
7. Biochemical tests should meet the following criteria: (1) Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value (ULN), or ≤2.5 times the upper limit of normal value (ULN) in the case of liver metastasis (2) alanine aminotransferase (ALT) and aspartate aminotransferase AST≤2.5 ×ULN, if accompanied by liver metastasis, ALT and AST≤5×ULN(3) Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr)≥60ml/min；
8. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ the lower limit of normal (50%)；
9. Patients of childbearing age (including female and female partners of male patients) must take effective birth control measures
10. he subjects volunteered to participate in this study and signed the ICF；
11. Good compliance is expected, and the efficacy and adverse reactions can be followed up according to the protocol requirements.

Exclusion Criteria:

1. Previous use of antiangiogenic drugs, such as bevacizumab, apatinib, anlotinib, lenvatinib and other antiangiogenic drugs
2. Previous treatment with more than one immune checkpoint inhibitor；
3. Patients who had previously interrupted treatment due to immune-related toxicity during immunotherapy；
4. Patients with severe history of allergy or allergic constitution；
5. Pregnant or lactating women；
6. Patients who have participated in other clinical trials and have not terminated the trial；
7. Patients with a definite propensity for gastrointestinal bleeding. Including the following conditions: ① local active ulcer lesions, and stool occult blood 2+ or abovePatients with fecal occult blood 2+ allowed to retest fecal occult blood and determined by the investigator to have a clear benefit could be enrolled) ② Patients with melena and hematemesis within 3 months； ③ Gastroscopy is required for patients with fecal occult blood 1+ and primary gastric tumor that has not been surgically resected, such as ulcerated gastric cancer, and major gastrointestinal bleeding may occur according to the main investigator of the center；
8. Patients with any severe and/or uncontrolled disease, including: (1) patients with poorly controlled blood pressure (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg)； (2) Patients with grade I or higher myocardial ischemia or infarction, arrhythmias (including QTc ≥ 480ms), or congestive heart failure grade 2 (New York Heart Association (NYHA) classification)； (3) Active or uncontrolled severe infection (≥CTC AE grade 2 infection)； (4) Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need antiviral therapy； (5) Renal failure requiring hemodialysis or peritoneal dialysis； (6) Have a history of immunodeficiency, including being HIV positive or suffering from other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation； (7) Two consecutive routine urine tests indicated urinary protein ≥++, and confirmed 24-hour urinary protein quantity \> 1.0 g； (8) suffer from mental illness, including epilepsy, dementia, severe depression, mania, etc
9. Receiving major surgical treatment, open biopsy or obvious traumatic injury within 28 days before grouping (body-body clinical evaluation)
10. Any history of active autoimmune disease or autoimmune disease, including but not limited to interstitial pneumonia, uveitis, inflammatory bowel disease, hepatitis, pituitary inflammation, vasculitis, systemic lupus erythematosus, etc.
11. Patients whose imaging showed that the tumor had invaded the periphery of important blood vessels or who were judged by the investigator to be highly likely to invade important blood vessels during the subsequent study and cause fatal massive bleeding；
12. Patients with any evidence of bleeding constitution or history, regardless of severity；Patients who had any bleeding or bleeding events ≥CTCAE grade 3 in the 4 weeks before enrollment had unhealed wounds, ulcers, or fractures；
13. 6 months have experienced an arteriovenous thrombotic event, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism；
14. Patients with brain metastases associated with symptoms or symptom control for less than 2 months；
15. Persons with a history of psychotropic drug abuse and inability to abstain or mental disorders；
16. Subjects with dysphagia or known drug absorption disorders；
17. Other conditions deemed inappropriate for inclusion by the investigator。

Where this trial is running

Changzhou, Jiangsu

• The First People's Hospital of Changzhou — Changzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: wu jun

Conditions Gastric Cancer