Clinical trial NCT05008861: Gut Microbiota Reconstruction for NSCLC Immunotherapy
Official title: Safety of Gut Microbiota Reconstruction Plus PD-1/PD-L1 Monoclonal Antibodies to Treat Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2021-08-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, patients with locally advanced or metastatic NSCLC after first-line treatment with PD-1/PDL-1 monoclonal antibody will be treated with Gut Microbiota reconstruction(such as FMT) combined with PD-1/PDL-1 monoclonal antibody. We will evaluate the safety of FMT in the treatment of advanced NSCLC, and analyze the effect of FMT on intestinal flora and immunophenotype of patients.


Eligibility criteria: Inclusion Criteria:

1.Volunteer to participate in this trial, fully understand this trial, and sign the Informed Consent Form (ICF).

2.18-75 years old on the day of signing the ICF. 3.Locally advanced/metastatic non-small cell lung cancer diagnosed by histology or cytology. no epidermal growth factor receptor (EGFR) sensitive mutations, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS Proto-oncogene 1 (ROS1) gene fusion.

4.Have stable disease (SD) defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after receive at least 2 doses of anti-PD-1/PD-L1 for first-line treatment.

5.Have not received systemic treatment for locally advanced/metastatic NSCLC before immunotherapy.

6.Have measurable target lesions judged by the investigator according to Response Evaluation Criteria In Solid Tumors (RECIST V1.1).

7.0\~1 ECOG score. 8.Life expectancy ≥ 12 weeks. 9.Have sufficient organ function, evaluated based on blood routine, renal function, liver function, and coagulation laboratory test results (and have not received blood transfusion or infusion of apheresis components within 14 days before the study drug administration , Erythropoietin, granulocyte colony stimulating factor and other medical support treatments).

10.Women of Childbearing Potential (WOBCP) must undergo a serum pregnancy test within 7 days before the first medication, and the result is negative; WOBCP or men and their WOBCP partners should agree from signing the ICF to the last one. Take effective contraceptive measures within 6 months after taking the study drug.

Exclusion Criteria:

1. Before the first administration of the anti-PD-1/PD-L1 reatment: a) have received previous systemic cytotoxic chemotherapy for metastatic disease; b) have received other targeted or biological anti-tumor therapy for metastatic disease ; c) received major surgery (\<3 weeks before the first dose); d) received lung radiotherapy \>30 Gy within 6 months before the first dose of the trial treatment; e) the first trial treatment Palliative radiotherapy was completed within 7 days before administration.
2. Any other form of anti-tumor therapy is expected during the study period.
3. Have progressive disease (PD) or response(CR or PR) defined by RECIST v1.1 after receive at least 2 doses of anti-PD-1/PD-L1 for first-line treatment.
4. Unable to tolerate anti-PD-1/PD-L1 treatment due to adverse events or other reasons.
5. Unable to swallow FMT capsules.
6. Received antibiotic treatment within 30 days before the planned FMT started.
7. Fecal occult blood test or calprotectin positive; have ulcerative colitis, Crohn's disease, ischemic enteritis, infectious enteritis, etc not suitable to take intestinal bacteria capsules, but not include anti-PD-1/PD-L1-related colitis.
8. Live virus vaccines have been vaccinated within 30 days before the planned treatment. Seasonal influenza vaccine without live virus is allowed.
9. A history of past malignant disease is known, unless the subject receives potentially curative treatment and there is no evidence of disease recurrence within 5 years after starting treatment.
10. Accompanying known active central nervous system (CNS) metastasis and/or cancerous meningitis.
11. According to the standard of Common Adverse Event Terminology (CTCAE) 4th edition, peripheral neuropathy has been ≥2 grade.
12. Severe hypersensitivity reactions to other monoclonal antibody treatments have occurred in the past.
13. Accompanied by active autoimmune diseases, systemic treatment (ie, use of disease modifiers, corticosteroids or immunosuppressive drugs) is required within the past 2 years.
14. Are receiving long-term systemic steroid therapy. Subjects with asthma who require intermittent use of bronchodilators, inhaled steroids, or topical steroid injections are not excluded.
15. Have received any other anti-PD-1 or PD-L1 or PD-L2 drugs or antibodies in the past, or small molecule therapy that targets other immunomodulatory receptors or mechanisms. Participated in any other anti-PD-1/PD-L1 trials and received anti-PD-1/PD-L1 treatment. Such antibodies include (but are not limited to) antibodies against IDO, PD-L1, IL-2R and GITR.
16. Active infections requiring treatment.
17. Known human immunodeficiency virus (HIV) history (known HIV1/2 antibody positive). Accompanied by known active hepatitis B or C.
18. Being pregnant or breastfeeding, or expecting to conceive or conceive during the period of study drug treatment and within the required contraceptive period after the last administration of the study drug.
19. The researcher believes that there are any circumstances that are not suitable for selection.

Primary outcomes:
measure: Incidence of FMT-related Adverse Events
timeFrame: 2 years
measure: Incidence of anti-PD-1/PD-L1-related Adverse Events
timeFrame: 2 years
Secondary outcomes:
measure: Changes in diversity and composition of gut microbiota
timeFrame: 2 years
measure: Efficiency of FMT engraftment
timeFrame: 2 years
measure: Changes in concentration of peripheral blood mononuclear cells
timeFrame: 2 years
measure: Changes in concentration of tumor immune related cytokines
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xizhong Shen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: