Efficacy and Safety of Fecal Microbiota Transplant(FMT) Combination With Tislelizumab in Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed After Prior Immune Checkpoint Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 主要终点
- Safety(SAE, AE)
研究概览
简要总结
This study aims to investigate the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment for non-small cell lung cancer (NSCLC) patients whose disease has progressed after immune checkpoint inhibitor (ICI) therapy, and to establish the foundation for personalized FMT through gut microbiome analysis.
Recovering immune responses in patients who have failed prior immunotherapy remains an unmet clinical need. This study aims to provide evidence to address this issue. Fecal microbiota transplantation (FMT) is a means that can rapidly and efficiently change the intestinal microbiota and has the potential to affect the systemic immune environment. Therefore, this study intends to contribute to the development of future treatment strategies by evaluating whether FMT can restore the immune response and clinical efficacy in patients with immune checkpoint inhibitor-resistant NSCLC.
详细描述
The most significant improvement in response rates has been demonstrated by whole microbiome intervention via fecal microbiota transplantation (FMT) has demonstrated the most significant improvement in response rates compared to individual species-based interventions.
In light of the established clinical efficacy of ICIs and FMT in patients with solid malignancies, a phase II study was designed to investigate the potential of FMT in restoring clinical efficacy in patients who have failed ICI treatment.
This study is planning to register 10 donors and 15 recipients.
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
- 是
入选标准
- •① Subjects who have voluntarily provided written Informed consent to participate in this clinical trial
- •② Aged of 19 or older
- •③ Subjects who meet one of the following criteria:
- •Patients with histologically confirmed NSCLC who have maintained a clinical benefit(partial response, PR) for more than 1 year through immune checkpoint inhibitor therapy
- •Healthy volunteers with no history of inflammatory bowel disease ④ Subjects who agree to provide repetitive blood and fecal samples during the trial period
- •RECIPIENT
- •Have voluntarily provided written Informed consent to participate in this clinical trial
- •Adults aged 19 years or older
- •Histologically or cytologically confirmed progressive or metastatic NSCLC
- •Subjects with at least one measurable lesion according to RECIST v1.1
- •Subjects who have received one or more chemotherapy treatments and have experienced disease progression after prior immunotherapy (However, patients with confirmed EGFR or ALK mutations must have shown progression after approved targeted therapies.)
- •Subjects with a life expectancy is at least 3 months ⑧ Subjects with adequate bone marrow and organ function within 14 days prior to study treatment, defined as:
- •Absolute neutrophil count (ANC): ≥ 1.5×109/L
- •Hemoglobin: ≥ 9.0 g/dL
- •Platelet count: ≥ 75×109/L
- •Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault
- •AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)
- •Total bilirubin: ≤ 1.5×ULN (< 3×ULN for Gilbert's syndrome(unconjugated hyperbilirubinemia) or liver metastases) ⑨ Female Subjects must be using a highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug ⑩ Male Subjects must be using highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug and refrain from sperm donation
- •⑪ Agreed to provide blood and fecal samples during the trial period
排除标准
- •Have voluntarily provided written Informed consent to participate in this clinical trial
- •Adults aged 19 years or older
- •Histologically or cytologically confirmed progressive or metastatic NSCLC
- •Subjects with at least one measurable lesion according to RECIST v1.1
- •Subjects who have received one or more chemotherapy treatments and have experienced disease progression after prior immunotherapy (However, patients with confirmed EGFR or ALK mutations must have shown progression after approved targeted therapies.) ⑥ ECOG 0-1
- •Subjects with a life expectancy is at least 3 months
- •Subjects with adequate bone marrow and organ function within 14 days prior to study treatment, defined as:
- •Absolute neutrophil count (ANC): ≥ 1.5×109/L
- •Hemoglobin: ≥ 9.0 g/dL
- •Platelet count: ≥ 75×109/L
- •Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault
- •AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)
- •Total bilirubin: ≤ 1.5×ULN (< 3×ULN for Gilbert's syndrome(unconjugated hyperbilirubinemia) or liver metastases)
- •Female Subjects must be using a highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug
- •Male Subjects must be using highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug and refrain from sperm donation
- •Agreed to provide blood and fecal samples during the trial period
- •RECIPIENT
- •Have voluntarily provided written Informed consent to participate in this clinical trial
- •Adults aged 19 years or older
- •Histologically or cytologically confirmed progressive or metastatic NSCLC
- •Subjects with at least one measurable lesion according to RECIST v1.1
- •Subjects who have received one or more chemotherapy treatments and have experienced disease progression after prior immunotherapy (However, patients with confirmed EGFR or ALK mutations must have shown progression after approved targeted therapies.)
- •ECOG 0-1 ⑦ Subjects with a life expectancy is at least 3 months
- •Subjects with adequate bone marrow and organ function within 14 days prior to study treatment, defined as:
- •Absolute neutrophil count (ANC): ≥ 1.5×109/L
- •Hemoglobin: ≥ 9.0 g/dL
- •Platelet count: ≥ 75×109/L
- •Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault
- •AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)
- •Total bilirubin: ≤ 1.5×ULN (< 3×ULN for Gilbert's syndrome(unconjugated hyperbilirubinemia) or liver metastases)
- •Female Subjects must be using a highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug ⑩ Male Subjects must be using highly effective method of contraception during the clinical trial and for 4months after permanent discontinuation of the study drug and refrain from sperm donation
- •Agreed to provide blood and fecal samples during the trial period
研究组 & 干预措施
Fecal Microbiota Transplant(FMT) combination with Tislelizumab
A fixed dose of 200mg Q3W Tislelizumab IV until PD And Q9W FMT (max 3)
干预措施: Tislelizumab (Drug)
Fecal Microbiota Transplant(FMT) combination with Tislelizumab
A fixed dose of 200mg Q3W Tislelizumab IV until PD And Q9W FMT (max 3)
干预措施: Fecal Microbiota Transplant(FMT) (Procedure)
结局指标
主要结局
Safety(SAE, AE)
时间窗: From enrollment to the EOT, up to 42 months
to evaluate the clinical safety (by NCI-CTCAE v5.0)
次要结局
- ORR(up to 42 months)
- OS(up to 42 months)
- PFS(up to 42 months)
- DCR(up to 42 months)
- DOR(up to 42 months)
研究者
Se-Hoon Lee
Principal Investigator
Samsung Medical Center