Perioperative Chemotherapy Combined With Serplulimab or Placebo for pMMR Locally Advanced Gastric Adenocarcinoma (FOCUS-05)

Perioperative S-1 Plus Oxaliplatin Combined With Serplulimab or Placebo for Locally Advanced Gastric Adenocarcinoma With Proficient Mismatch Repair: a Prospective, Multi-center, Double-blinded, Randomized Placebo-controlled Study

This phase II study is a prospective, multi-center, double-blinded, and randomized trial to compare the efficacy and safety of perioperative SOX plus serplulimab with SOX plus placebo for locally advanced gastric adenocarcinoma with proficient mismatch repair

Study Overview

• Status: Recruiting
• Conditions: Adenocarcinoma of the Stomach; Adenocarcinoma of Esophagogastric Junction; Proficient Mismatch Repair
• Intervention / Treatment: Drug: Oxaliplatin; Drug: S1; Drug: Serplulimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 314
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiren Yu; Phone Number: +86-0571-87236147; Email: yujr0909@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Jiren Yu
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • The Second Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Jian Chen
    • Lishui, Zhejiang, China, 323000
      • Not yet recruiting
      • Lishui Central Hospital
      • Contact: Hongtao Xu
    • Ningbo, Zhejiang, China, 315048
      • Not yet recruiting
      • Ningbo medical center lihuili hospital
      • Contact: Weiming Yu
    • Taizhou, Zhejiang, China, 317099
      • Not yet recruiting
      • Taizhou Hospital
      • Contact: Shenkang Zhou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the Informed Consent Form (ICF).
2. The gender is not limited. Age: ≥ 18 years and ≤ 80 years old.
3. Gastric or esophagogastric junction adenocarcinoma confirmed by pathology, and proficient mismatch repair confirmed by immunohistochemistry.
4. Clinical stage at presentation: cT2-T4b, N+/-, M0 as determined by AJCC staging system, 8th edition.The definition of metastatic lymph nodes: a lymph node must be ≥ 10mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm) according to the guideline of Response Evaluation Criteria in Solid Tumours (RECIST version 1.1)
5. Participants with a performance status of 0 ~ 1 on the Eastern Cooperative Oncology Group (ECOG) within 7 days before the first dose of study treatment.
6. Life expectancy ≥ 6 months.
7. Agreement of providing pretreatment endoscopic biopsies specimens and surgical specimens for biomarker analysis, as well as the peripheral blood, feces and urine sample.

8. The functions of the vital organs meet requirements as follow (within 14 days before the first dose of study treatment, participant has not received treatment of recombinant human thrombopoietin or granulocyte stimulating factor):

   8.1 Hematological function： White blood cell count (WBC): 3.5 × 10 ^ 9 / L ~12.0 × 10 ^ 9 / L； Absolute neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L； Platelet count (PLT) ≥ 100 × 10 ^ 9 / L； Hemoglobin (Hb) ≥ 90 g / L.

   8.2 Hepatic function： Total bilirubin (TBIL) ≤ 1.5 × ULN (upper limit of normal); Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN; Albumin (ALB) ≥ 30 g / L.

   8.3 Renal function： Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml / min for those with creatinine level > 1.5 × ULN.

   8.4 Coagulation function： International normalized ratio (INR) ≤ 1.5; Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

9. Female of childbearing age must meet requirements: urine or serum pregnancy test must be negative within 7 days before the first dose of study treatment, and she must agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of serplulimab, or 180 days after the last dose of chemotherapy, whichever is longer, and should not be breastfeeding.
10. For the male participants must meet requirements: agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of serplulimab, or 180 days after the last dose of chemotherapy, whichever is longer).

Exclusion Criteria:

1. HER2-positive, EBER-positive or dMMR.
2. Prior systemic therapy for treatment of gastric cancer (surgery, chemotherapy, radiotherapy, targeted therapy or immunotherapy).
3. Previous or concurrent have other active malignant tumors within the past 5 years (except for basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate cancer or cervical cancer or breast cancer in situ that has undergone curative therapy).
4. Participants with gastric outlet obstruction, or unable for oral take, or severe gastrointestinal bleeding.
5. Myocardial infarction within 6 months before the first dose of study treatment, uncontrolled angina, arrhythmia which need medical intervention (including but not limited to cardiac pacemaker), congestive heart failure (New York Heart Association (NYHA) class III or IV).
6. Existence of chronic diarrhea (watery diarrhea: ≥ 5 times per day).
7. Participants with active infection within 14 days before the first dose of study treatment which need medical intervention.
8. Participants with active tuberculosis.
9. Previous or concurrent diagnosed with interstitial lung disease by imaging or symptoms.
10. Any of the following test is positive: Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibody.
11. Participants who need long-term systemic steroid therapy (> 10 mg/d prednisone equivalent) or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment or during the study period.
12. Concurrent or previous have severe allergic reaction to any antibody-based drugs.
13. Existence of any concurrent autoimmune disease, excepting participants with diabetes mellitus type I, hypothyroidism requiring only hormone replacement therapy.
14. Receive live vaccines within 28 days before the first dose of study treatment or during the study period, excepting inactivated viral vaccines for seasonal influenza.
15. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
16. Existence of systemic disease that is difficult to control despite treatment with several agents, for example, diabetes mellitus, hypertension, etc.
17. Existence of other serious physical or mental diseases or serious laboratory abnormalities that may increase the risk of participating in the study. Participants who were judged unsuitable as subjects of this trial by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (Chemotherapy+Serplulimab ); Drug: Oxaliplatin，S-1，Serplulimab Chemotherapy (SOX): Oxaliplatin, administered as a 2-hour intravenous infusion (130 mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery. Serplulimab: 300 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery.	Drug: Oxaliplatin; Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy; Drug: S1; S-1 orally intake as perioperative chemotherapy; Drug: Serplulimab; Perioperative serplulimab, 300 mg IV infusion
Active Comparator: Group B (Chemotherapy+Placebo ); Drug: Oxaliplatin，S-1，Placebo Chemotherapy (SOX): Oxaliplatin, administered as a 2-hour intravenous infusion (130 mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery. Placebo: 300 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery.	Drug: Oxaliplatin; Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy; Drug: S1; S-1 orally intake as perioperative chemotherapy; Drug: Placebo; Perioperative placebo, 300 mg IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathological complete responses (pCR)	Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.	From enrollment to surgery after pre-operative treatment (up to approximately 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) will be defined as the time from enrollment to the end of follow up or the time of disease progression or relapse or death from any cause	From enrollment to the end of follow up or the time of disease progression or relapse or death from any cause (up to approximately 60 months)
Overall survival	Overall survival (OS) will be determined by measuring the time interval from enrollment to the end of follow up or death from any cause	From enrollment to the end of follow up or death from any cause (up to approximately 60 months)
The incidences and types of adverse events (AE) and severe adverse events (SAE)	The incidences and types of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	From enrollment to 90-day after the last dose administration (up to approximately 27 months)

Collaborators and Investigators

• Sponsor: Yu jiren

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: May 14, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Gastric Adenocarcinoma; Perioperative Chemotherapy; Serplulimab; Proficient mismatch repair
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: IIT20230020C-R1

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