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.

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.

Inclusion Criteria:

• DONOR

  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:

  1. Patients with histologically confirmed NSCLC who have maintained a clinical benefit(partial response, PR) for more than 1 year through immune checkpoint inhibitor therapy
  2. 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.)

            • ECOG 0-1

              • 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:

                1. Absolute neutrophil count (ANC): ≥ 1.5×109/L

                2. Hemoglobin: ≥ 9.0 g/dL

                3. Platelet count: ≥ 75×109/L

                4. Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault

                5. AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)

                6. 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

Exclusion Criteria:

• DONOR

  • 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:

                1. Absolute neutrophil count (ANC): ≥ 1.5×109/L

                2. Hemoglobin: ≥ 9.0 g/dL

                3. Platelet count: ≥ 75×109/L

                4. Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault

                5. AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)

                6. 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:

                1. Absolute neutrophil count (ANC): ≥ 1.5×109/L

                2. Hemoglobin: ≥ 9.0 g/dL

                3. Platelet count: ≥ 75×109/L

                4. Serum creatinine ≤ 1.5×ULN or CrCl ≥ 30 mL/min as determined by Cockcroft-Gault

                5. AST(SGOT)/ALT(SGPT): ≤ 3×ULN (≤ 5×ULN in the presence of liver metastases)

                6. 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