FMT+Immunotherapy+Chemotherapy as First-line Treatment for Driver-gene Negative Advanced NSCLC

Trial Title: FMT+Immunotherapy+Chemotherapy as First-line Treatment for Driver-gene Negative Advanced NSCLC

NCT ID: NCT06403111

Condition: Non-small Cell Lung Cancer

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Immunomodulating Agents

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Combination Product
Intervention name: Fecal Microbiota Transplantation (FMT)+chemotherapy+immunotherapy
Description: Participants received FMT combined with tislelizumab + pemetrexed and platinum-based therapy (for adenocarcinoma patients) / albumin-bound paclitaxel and platinum-based therapy (for squamous cell carcinoma patients).
Arm group label: Chemotherapy+Immunotherapy+FMT

Summary: This study plans to reconstruct intestinal microecology through fecal microbiota transplantation (FMT), and combine first-line standard therapy to enhance the anti-tumor immune effect at the same time, thereby extending the progression-free survival of patients and improving the prognosis of patients.

Detailed description: This is a prospective, single-arm, multicenter, exploratory clinical study. That is, eligible patients with driver-gene negative, ECOG PS 0-1, PD-L1<50% advanced non-small cell lung cancer who have not received prior treatment will be screened after signing informed consent and receive FMT combined with tislelizumab + pemetrexed and platinum-based therapy (for adenocarcinoma patients) / albumin-bound paclitaxel and platinum-based therapy (for squamous cell carcinoma patients). RECIST v1.1 was used for tumor evaluation every 6 weeks during treatment. NCI-CTCAE 5.0 was used for safety assessment every 3 weeks. Adverse events were recorded throughout the study to 30 days after the end of treatment. Treatment continues until disease progression, subject withdraws informed consent, loss of follow-up, or death. Patients should provide 10ml whole blood samples and fecal samples at baseline, after two cycles of treatment, before maintenance treatment, and after two cycles of maintenance treatment for the detection of efficacy prediction markers (each cycle is 21 days).

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. The subjects voluntarily joined the study and were able to sign the informed consent with good compliance; 2. Age 18-80 years old (when signing the informed consent form); 3. Patients with histologically or cytologically proven locally advanced (stage IIB/IIC), metastatic, or recurrent (stage IV) NSCLC who are inoperable and unable to receive radical concurrent chemoratherapy, according to the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification, 8th Edition TNM Classification of Lung cancer; 4. Have not received systemic intravenous anti-tumor therapy before, and the driver gene is negative; 5. PD-L1 expression < 50%; 6. According to the solid tumor efficacy evaluation criteria (RECIST version 1.1), there is at least one radiographically measurable lesion; That is, in CT or MRI detection, the longest diameter of a single lesion was ≥10mm, or the pathological enlargement of a single lymph node was ≥15mm. 7. The physical status score of Eastern Tumor Collaboration Group (ECOG) was 0-1; 8. Expected survival > 3 months; 9. Have adequate organ and bone marrow function, laboratory examination within 7 days prior to enrollment meets the following requirements (no blood components, cell growth factors, albumin or other corrective drugs are allowed within 14 days prior to obtaining laboratory examination), as follows: 1) Blood routine: absolute neutrophil count (ANC) ≥1.5×109/L, platelet (PLT) ≥75×109/L, hemoglobin (HGB) ≥90 g/L (no blood transfusion or erythropoietin dependence within 14 days); 2) Liver function: serum total bilirubin (TBIL) ≤2 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 5x ULN, serum albumin ≥28 g/L; alkaline phosphatase (ALP) ≤5×ULN; 3) Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (using the standard Cockcroft-Gault formula) : Urine routine results showed urinary protein < 2+; For patients with urine protein ≥2+ at baseline, 24-hour urine collection and 24-hour urine protein quantification < 1g should be performed. 4) Coagulation function: International standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN; If the subject is receiving anticoagulant therapy, as long as the INR is within the intended range of anticoagulant drug use. 10. For female subjects of reproductive age, a urine or serum pregnancy test should be performed and the result is negative 3 days prior to receiving the initial study drug administration; 11. Subjects and their sexual partners are required to use a medically approved contraceptive method (such as an IUD, contraceptive pill, or condom) during the study treatment period and for 6 months after the end of the study treatment period. Exclusion Criteria: 1. Currently participating in an interventional clinical study or receiving another investigational drug or investigational device within 4 weeks prior to initial dosing; 2. Received proprietary Chinese medicines with anti-tumor indications or immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first administration, or received major surgical treatment within 3 weeks before the first administration; 3. Class III - IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias; 4. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before treatment; 5. Known allergic reaction to the drug in this study; 6. Patients requiring long-term systemic use of corticosteroids. Patients with COPD or asthma requiring intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroids could be enrolled. 7. Symptomatic central nervous metastases. Patients with asymptomatic BMS or BMS whose symptoms are stable after treatment are eligible to participate in this study if they meet all of the following criteria: measurable lesions outside the central nervous system; No midbrain, pontine, cerebellum, meninges, medulla oblongata or spinal cord metastasis; Maintain clinical stability for at least 2 weeks; Stop hormone therapy 3 days before the first dose of the study drug; 8. There is an active infection requiring treatment or systemic anti-infective drugs have been used in the week prior to the first dosing; 9. Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss); 10. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 11. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected greater than the upper limit of normal value in the laboratory of the study center); Note: Hepatitis B subjects who meet the following criteria can also be enrolled: 1. HBV viral load <1000 copies /ml (200 IU/ml) before initial administration, subjects should receive anti-HBV therapy throughout the study chemotherapy drug treatment to avoid viral reactivation; 2. For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required. 12. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 13. Received live vaccine within 30 days prior to the first dose (cycle 1, day 1); Note: Injectable inactivated virus vaccine against seasonal influenza is permitted for 30 days prior to initial administration; However, live attenuated influenza vaccines administered intranasally are not permitted. 14. Pregnant or lactating women; 15. Medical history or evidence of disease that may interfere with test results, prevent participants from fully participating in the study, abnormal treatment or laboratory test values, or other conditions that the investigator considers unsuitable for enrollment The Investigator considers other potential risks unsuitable for participation in the study.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: Accepts Healthy Volunteers

Start date: June 1, 2024

Completion date: June 1, 2026

Lead sponsor:
Agency: Changzhou No.2 People's Hospital
Agency class: Other

Source: Changzhou No.2 People's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06403111