A Phase Ib/II Study of First Line Pembrolizumab in Combination With Trastuzumab, Capecitabine, and Cisplatin in HER2 Positive Gastric Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- The recommended dose of phase II
研究概览
简要总结
Gastric cancer is one of the major health problems worldwide, and one of the leading cause of death especially in Asia. Though the cytotoxic chemotherapy is the main treatment option, newer and molecularly targeted agents are recently incorporated to improve the survival outcome. Human epidermal growth factor receptor 2 (HER2, ErbB2) is a transmembrane tyrosine kinase receptor and is overexpressed or amplified in 10-20% of gastric cancer. Recently, Trastuzumab for Gastric Cancer (ToGA) study reported the clinical benefit of trastuzumab for HER2 positive gastric cancer patients. However, because the majority of patients develop intrinsic or acquired resistance within 1 year, elucidating the molecular mechanisms for trastuzumab resistance is warranted to improve the survival outcome of HER2 positive gastric cancer patients.
A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of "monoclonal antibody, trastuzumab" in solid tumors. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Based on strong rationale in exploring the impact of combining trastuzumab with anti-PD-1 inhibitor in HER2 positive cancer, we suggest multicenter phase IB/II study to determine antitumor activity and safety of pembrolizumab in combination with standard treatment (trastuzumab, capecitabine, and cisplatin) in patients with HER2 positive gastric cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HER2 positive advanced gastric cancer
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be 19 years of age on day of signing informed consent.
- •Have measurable disease based on RECIST 1.
- •performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
- •Demonstrate adequate organ function
- •Female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control.
排除标准
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active Bacillus Tuberculosis
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent.
- •Has a known additional malignancy that is progressing or requires active treatment within 3 years.
- •Has known active central nervous system metastases and/or carcinomatous meningitis.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years
- •Has known history of, or any evidence of active, non-infectious pneumonitis.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- •Has known active Hepatitis B or Hepatitis C
- •Has received a live vaccine within 30 days of planned start of study therapy.
研究组 & 干预措施
4 combination
pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1
干预措施: Pembrolizumab (Drug)
4 combination
pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1
干预措施: Trastuzumab (Drug)
4 combination
pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1
干预措施: Capecitabine (Drug)
4 combination
pembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1
干预措施: Cisplatin (Drug)
结局指标
主要结局
The recommended dose of phase II
时间窗: 4 weeks
The overall response rate using RECIST 1.1
时间窗: 6 weeks
次要结局
- Duration of response(1 year)
- Time to response(6 weeks)
研究者
Hyun Cheol Chung
Professor
Yonsei University