Combining PD-1 blockade with chemotherapy for gastric cancer treatment

An Open, Single-center, Phase II Clinical Trial Evaluating the Efficacy of PD-1 Antibody (JS001) in Combination With Neoadjuvant Chemotherapy for Gastric/Gastroesophageal Junction Cancer

This study is testing if a new combination of a cancer drug and chemotherapy can help people with advanced stomach cancer respond better to treatment before and after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Ages: 18 Years to 79 Years
• Sex: All
• Sponsor: Shenzhen People's Hospital (other)
• Drugs / interventions: toripalimab, nivolumab, pembrolizumab, chemotherapy
• Locations: 2 sites (Shenzhen, Guangdong and 1 other locations)
• Trial ID: NCT05033392 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial evaluates the effectiveness of toripalimab, a PD-1 antibody, in combination with the FLOAP chemotherapy regimen for patients with locally advanced gastric and gastroesophageal junction cancer. Participants will receive four cycles of this treatment before surgery, followed by additional cycles post-surgery. The primary goal is to assess the rate of pathological complete response (pCR), while secondary outcomes include disease-free survival (DFS), overall survival (OS), and the rate of complete surgical resection. The study aims to improve treatment outcomes for patients with this aggressive cancer type.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 79 with confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma.

Not a fit: Patients with early-stage gastric cancer or those who cannot provide adequate tumor tissue samples may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with advanced gastric cancer.

How similar studies have performed: Previous studies have shown promising results with PD-1 blockade combined with chemotherapy in advanced gastric cancer, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 yeas and ≤79 years. The gender is not limited.
2. Confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination.
3. Endoscopic ultrasonography and/or enhanced CT/MRI examination confirmed at the stage of cT3/4a Nx or T2 N1-3, M0(AJCC 8th) before randomization.
4. At least 15 unstained sections of formalin-fixed paraffin-embedded tumor tissue sections or fresh tumor tissues can be provided for PD-L1, TMB, tumor infiltrating T lymphocytes, MSI-H/dMMR and EBV detection.
5. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1
6. Adequate bone marrow and organ function meets the following criteria:

   1. Neutrophil count (ANC)≥1.5×l09/L
   2. Platelet (PLT) ≥80×109/L
   3. Hemoglobin (Hb) level ≥9.0 g/L
   4. Total bilirubin level≤1.5×ULN
   5. Alanine aminotransferase (ALT) level≤3×ULN
   6. Aspartate aminotransferase (AST) level ≤3×ULN
   7. International normalized value (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN
   8. Serum creatinine (Cr) level ≤1.5×ULN
   9. Creatinine clearance \>50 ml/min (Calculated according to the Cockcroft-Gault formula)

Exclusion Criteria:

1. Patients with a history of severe hypersensitivity to other monoclonal antibodies or any component of toripalimab injection (JS001).
2. Preoperative pathology diagnosed as squamous cell carcinoma or neuroendocrine tumor.
3. Patients have experienced or currently have other malignancies within 5 years.
4. Patients have received prior therapy with anti-PD-1, anti-PD-L1 or anti-CTLA4 agent.
5. Patients with history of autoimmune disease; patients with autoimmune-related hypothyroidism receive stable doses of thyroid hormone replacement therapy Eligible to participate in this study; Type 1 diabetes patients who are controlled after receiving a stable insulin treatment plan are eligible to participate in this study;
6. Patients have received systemic immunostimulatory drug therapy (including but not limited to interferon or IL-2) within 4 weeks before enrollment or within 5 half-lives of the drug (whichever is shorter);
7. Patients who have undergone allogeneic bone marrow transplantation or solid organ transplantation in the past;
8. Active infections, including tuberculosis (clinical diagnosis includes clinical history, physical examination and imaging findings, and TB examination according to local medical routines), hepatitis B {known HBV surface antigen (HBsAg) positive, and HBV DNA ≥1000cps/ml}, hepatitis C or human immunodeficiency virus (HIV antibody positive).
9. Patients with previous or cured HBV infection (defined as hepatitis B core antibody \[anti-HBc\] positive and HbsAg negative) are only eligible to participate in this study when HBV DNA is negative (HBV DNA ˂1000cps/ml).
10. Patients with positive hepatitis C (HCV) antibodies are only eligible to participate in this study if the polymerase chain reaction shows negative HCV RNA.
11. There is a serious neurological or mental illness, including dementia and seizures.
12. Suffer from NCI-CTCAE ≥ Grade 2 peripheral neuropathy.
13. Women who are pregnant or breastfeeding.
14. Chronic bowel disease or short bowel syndrome.
15. Those who are deficient in the enzyme dihydropyrimidine dehydrogenase (DPD).
16. Major cardiovascular diseases, such as New York Heart Association heart disease (level II or higher), myocardial infarction within 3 months before randomization, unstable arrhythmia, or unstable angina.
17. Patients with known coronary artery disease, congestive heart failure that does not meet the above criteria, or left ventricular ejection fraction \<50% must adopt an optimized and stable medical plan determined by the treating doctor. If necessary, you can consult a cardiologist.

Where this trial is running

Shenzhen, Guangdong and 1 other locations

• Shenzhen People's Hospital — Shenzhen, Guangdong, China (RECRUITING)
• Shenzhen People's Hospital — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Wan He, PhD — Shenzhen People's Hospital
• Study coordinator: Wan He, PhD

Conditions: Stomach Neoplasms, PD-1 antibody, neoadjuvant chemotherapy, gastric cancer, gastroesophageal junction cancer