A Phase 2, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 15
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine whether CRS-207 in combination with pembrolizumab is safe and effective in adults with recurrent or metastatic gastric, gastroesophageal junction, or esophageal cancer who have received one or two prior chemotherapy regimens for advanced disease.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis with confirmed histology of one or more of the following:
- •Histologically-confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma (Siewert type II/III classification), or
- •Histologically-confirmed inoperable superior, medial, or distal third esophageal adenocarcinoma (Siewert type I classification may be included, provided there is no mixed histology)
- •Confirmed recurrent or metastatic disease
- •Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.
- •HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Can provide tissue for PD-L1 and mesothelin biomarker analysis
- •Adequate organ and marrow function at screening
排除标准
- •Diagnosis of squamous or undifferentiated gastric cancer
- •Individuals with inaccessible tumors or for whom biopsy is contraindicated
- •Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of first dose of study drug
- •Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
- •Clinical evidence of ascites by physical exam
- •Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug or has not recovered from adverse effects due to agents administered more than 4 weeks earlier
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug, or has not recovered from adverse effects due to a previously-administered agent
- •Subjects who have implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g. artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g. Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.
研究组 & 干预措施
CRS-207 + Pembrolizumab
CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.
干预措施: CRS-207 (Biological)
CRS-207 + Pembrolizumab
CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) \> partial response (PR) \> stable disease (SD) \> progressive disease (PD) \> not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. .
次要结局
- Disease Control Rate (DCR)(BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.)
- Progression-Free Survival (PFS)(Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.)
- Duration of Response (DOR)(DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.)
- Overall Survival (OS)(OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 15 weeks.)