A Prospective, Multicenter, Phase II Clinical Study of First-line Treatment for HER2 (human Epidermal Growth Factor Receptor 2) Positive Advanced Gastric Cancer with Disitamab Vedotin in Combination with Tirelizumab and S-1
Overview
- Phase
- Phase 2
- Intervention
- Disitamab vedotin
- Conditions
- HER2-positive Gastric Cancer
- Sponsor
- Qilu Hospital of Shandong University
- Enrollment
- 55
- Locations
- 7
- Primary Endpoint
- objective response rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a prospective, single arm, multicenter phase II study aimed at evaluating the efficacy and safety of Disitamab Vedotin in Combination With Tirelizumab and S-1 as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged18-75 years, gender is not limited;
- •Pathologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma that is inoperable or has distant metastasis;
- •HER2 was detected as 2+or 3+ by immunohistochemistry（IHC） ;
- •Has at least 1 measurable lesion as determined by RECIST 1.1;
- •There is no systematic treatment in the past, or the patient has received neoadjuvant/adjuvant chemotherapy, but the disease progresses or relapses more than 6 months after the end of treatment;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- •Adequate organ function:
- •Bone marrow function: i. Hemoglobin count (HGB)≥80g/L; ii. Neutrophil count (NE)≥1.5×109/L; iii. White blood cell count (WBC)≥3.5×109/L; iv. Platelet count (PLT)≥100×109/L；
- •Liver function: i. Serum total bilirubin (TBIL)≤1.5×ULN; ii. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)≤3×ULN, patients with liver metastasis≤5×ULN;
- •Kidney function: Blood creatinine (Cr) ≤1.5×ULN or Cockcroft Gault formula ≥ 60 mL/min;
Exclusion Criteria
- •Allergy to any trial drug and its excipients, or serious allergy history, or contraindication of the trial drug;
- •Cardiovascular and cerebrovascular events that are not well controlled, such as:
- •NYHA grade 2 or above heart failure;
- •Unstable angina pectoris;
- •Myocardial infarction occurred within 1 year;
- •Supraventricular or ventricular arrhythmia with clinical significance needs treatment or intervention;
- •Cerebral hemorrhage and cerebral infarction (except for lacunar cerebral infarction without symptoms and without treatment);
- •Serious cardiovascular and cerebrovascular events occurred within 12 months;
- •Uncontrolled hypertension, i.e. systolic blood pressure\>140 mmHg or diastolic blood pressure\>90 mmHg after single drug treatment;
- •Patients with history of arterial thrombosis or deep vein thrombosis within 6 months before recruitment, or with evidence of bleeding tendency or medical history within 2 months before recruitment, regardless of the severity;
Arms & Interventions
RC48 Plus Tislelizumab and S-1(RCTS)
Disitamab Vedotin: 2.5mg/kg, ivdrip, d1, (every 3 weeks) Q3W； Tislelizumab: 200mg, ivdrip, d1, (every 3 weeks) Q3W； S-1: 40-60mg(according to patients' body surface area), po, bid, d1-14 and discontinued for 7 days in each cycle; until progressive disease (PD) or intolerable toxicity
Intervention: Disitamab vedotin
RC48 Plus Tislelizumab and S-1(RCTS)
Disitamab Vedotin: 2.5mg/kg, ivdrip, d1, (every 3 weeks) Q3W； Tislelizumab: 200mg, ivdrip, d1, (every 3 weeks) Q3W； S-1: 40-60mg(according to patients' body surface area), po, bid, d1-14 and discontinued for 7 days in each cycle; until progressive disease (PD) or intolerable toxicity
Intervention: Tislelizumab
RC48 Plus Tislelizumab and S-1(RCTS)
Disitamab Vedotin: 2.5mg/kg, ivdrip, d1, (every 3 weeks) Q3W； Tislelizumab: 200mg, ivdrip, d1, (every 3 weeks) Q3W； S-1: 40-60mg(according to patients' body surface area), po, bid, d1-14 and discontinued for 7 days in each cycle; until progressive disease (PD) or intolerable toxicity
Intervention: S1
Outcomes
Primary Outcomes
objective response rate (ORR)
Time Frame: 6 months after the last subject participating in
The proportion of subjects with complete response (CR) and partial response (PR) in total subjects
Secondary Outcomes
- overall survival (OS)(12 months after the last subject participating in)
- duration of response (DOR)(12 months after the last subject participating in)
- progression-free survival (PFS)(12 months after the last subject participating in)
- disease control rate (DCR)(12 months after the last subject participating in)