Combining Serplulimab with Chemotherapy for Advanced Gastric Cancer Treatment

Efficacy and Safety of Serplulimab Combined With Nab-paclitaxel and SOX as Neoadjuvant Treatment for Locally Advanced Gastric Cancer or Adenocarcinoma of Esophagogastric Junction: A Multicenter Randomized Controlled Trial

This study is testing if adding a new immune treatment called serplulimab to standard chemotherapy can help people with advanced stomach cancer respond better to their treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Xijing Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, serlulimab, Nivolumab, Pembrolizumab, Srulizumab, radiation
• Locations: 5 sites (Shijiazhuang, Heibei Province and 4 other locations)
• Trial ID: NCT06576921 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of serplulimab, an immune checkpoint inhibitor, combined with nab-paclitaxel and SOX chemotherapy as a neoadjuvant treatment for patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction. It is a multicenter, double-blind, randomized phase 2 trial that aims to determine if this combination increases the rate of pathologic complete response (pCR) compared to chemotherapy alone. Participants will receive either the treatment with serplulimab or a placebo alongside standard chemotherapy, with safety and efficacy being closely monitored throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction who are eligible for surgical treatment after neoadjuvant chemotherapy.

Not a fit: Patients with metastatic gastric cancer or those with severe comorbidities that preclude participation in chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with advanced gastric cancer by enhancing the effectiveness of chemotherapy.

How similar studies have performed: Other studies have shown promising results with similar combinations of immune checkpoint inhibitors and chemotherapy, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age older than 18 and younger than 75 years
* Primary GC or AEG (Siewert II/III)confirmed pathologically by endoscopic biopsy
* Clinical stage T3/T4N+M0 disease as assessed by CT/MRI, PET-CT, and laparoscopy, if feasible
* At least one measurable lesion according to the RECIST, version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Surgical treatment after neoadjuvant chemotherapy is planned according to clinical staging criteria.
* Life expectancy of at least 3 months
* Acceptable bone marrow, hepatic, and renal function, including: a)Blood routine examination(No blood transfusion within 14 days; No granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors were used): white blood cell count ≥3.5 ×109/L, neutrophils ≥1.5 × 109/L, platelet count \>100 × 109/L, and hemoglobin ≥90 g/L; b)Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT and AST≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome patients, ≤3×ULN); c)Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥60mL/ min; d)Coagulation function: activated partial thromboplastin time (APTT), international standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
* Written informed consent

Exclusion Criteria:

* Squamous cell carcinoma, adenosquamous cell carcinoma, small cell carcinoma, and undifferentiated gastric cancer were confirmed by pathology
* Positive Her-2 detection (IHC3+ or IHC2+ amplified by FISH detection)
* Prior chemotherapy, radiotherapy, hormone therapy, targeted therapy, or immunotherapy
* Contraindications for surgical treatment or chemotherapy
* Presence of distant metastasis
* History of other malignant disease within the past 5 years, except: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that have been treated radically and have shown no signs of disease for at least 5 years
* Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
* History of immunodeficiency diseases, including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or transplantation
* Severe mental disorder
* Presence of digestive tract obstruction, jaundice, acute infectious diseases, inflammatory bowel disease, Crohn's disease, ulcerative colitis, chronic diarrhea, active tuberculosis
* Immunosuppressive drugs are required for 2 weeks or within 2 weeks or during the study period, excluding the following: a) intranasal, inhaled, topical or topical steroid injections (e.g. intra-articular injections); b) Physiological dose of systemic corticosteroids (≤10mg/ day prednisone or equivalent dose); c) Short-term (≤7 days) use of steroids for the prevention or treatment of non-autoimmune allergic diseases;
* Patients who have undergone major surgery or received live virus vaccine within 4 weeks
* Pregnant or breast-feeding women, subjects who are unwilling to receive effective contraception during treatment and within 6 months after the end of treatment (including male subjects who have the ability to impregnate women and female subjects and their male partners)
* Evidence of bleeding tendency or receiving thrombolytics or anticoagulants
* According to the criteria of the term Common Adverse Events (NCI-CTCAE V5.0), the corresponding symptoms have been diagnosed;
* Hepatitis B or hepatitis C virology tests at the time of screening meet any of the following: a) HBsAg positive and HBV-DNA titer ≥104 copy number /mL or ≥2000IU/mL (hepatitis B carriers should ask researchers for appropriate antiviral treatment); b) Active hepatitis C: HCV antibody positive and HCV-RNA higher than the lower detection limit of the assay;
* Allergic to study drugs
* The investigator believes that the subjects have other conditions that may affect their adherence to the protocol and evaluation of the study indicators, and the subjects are not suitable to participate in the study.

Where this trial is running

Shijiazhuang, Heibei Province and 4 other locations

• The fourth hospital of Hebei Medical University — Shijiazhuang, Heibei Province, China (Recruiting)
• Department of Digestive surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi' an, China — Xi'an, Shaanxi, China (Recruiting)
• Department of General Surgery, Tangdu Hospital, Air Force Medical University — Xi'an, Shaanxi, China (Recruiting)
• Department of General Surgery, The 986th Military Hospital, Air Force Medical University — Xi'an, Shaanxi, China (Recruiting)
• Tianjin Medical University Cancer Institute & Hospital — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Liu Hong, Ph.D — Xijing Hospital of Digestive Diseases, Xijing Hospital, Air force Medical University, Changlexi ST 15, Shaanxi Province, 710032, China
• Study coordinator: Zhenshun Li, Ph.D

Conditions Stomach Neoplasms; Immune Checkpoint Inhibitors; Gastric cancer; Adenocarcinoma of Esophagogastric junction cancer; PD-1 antibody