Gut Microbiota Reconstruction for NSCLC Immunotherapy

NCT05008861 | Unknown Phase 1

• 1 other identifier: B2021-179R
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of FMT-related Adverse Events

  Number of patients with adverse events after FMT

  2 years

• Incidence of anti-PD-1/PD-L1-related Adverse Events

  Number of patients with adverse events related to anti-PD-1/PD-L1 after FMT

  2 years

Secondary Outcomes (5)

• Changes in diversity and composition of gut microbiota

  2 years

• Efficiency of FMT engraftment

  2 years

• Changes in concentration of peripheral blood mononuclear cells

  2 years

• Changes in concentration of tumor immune related cytokines

  2 years

• Objective response rate (ORR)

  2 years

Study Arms (1)

FMT with anti-PD-1/PD-L1 treatment

EXPERIMENTAL

Procedure: Capsulized Fecal Microbiota Transplant; Drug: Anti-programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody; Drug: Platinum based chemotherapy

Interventions

Capsulized Fecal Microbiota Transplant PROCEDURE

Capsules contained washed fecal microbiota.

Also known as: Capsulized FMT

FMT with anti-PD-1/PD-L1 treatment

Anti-programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody DRUG

Standard dose of one of anti-PD-1/PD-L1 mAbs administered as a 1 hour infusion every 3 weeks.

Also known as: Anti-PD-1/PD-L1 mAb, Anti-PD-1/PD-L1, Pembrolizumab, Nivolumab, Durvalumab, Sintilimab, Tislelizumab, Camrelizumab

FMT with anti-PD-1/PD-L1 treatment

Platinum based chemotherapy DRUG

Standard dose of Platinum based Chemotherapy every 3 weeks.

Also known as: Platinum based Chemotherapy drugs

FMT with anti-PD-1/PD-L1 treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participate in this trial, fully understand this trial, and sign the Informed Consent Form (ICF).
• 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.
• 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.
• Have not received systemic treatment for locally advanced/metastatic NSCLC before immunotherapy.
• Have measurable target lesions judged by the investigator according to Response Evaluation Criteria In Solid Tumors (RECIST V1.1).
• \~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).
• 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.

You may not qualify if:

• 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.
• Any other form of anti-tumor therapy is expected during the study period.
• 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.
• Unable to tolerate anti-PD-1/PD-L1 treatment due to adverse events or other reasons.
• Unable to swallow FMT capsules.
• Received antibiotic treatment within 30 days before the planned FMT started.
• 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.
• Live virus vaccines have been vaccinated within 30 days before the planned treatment. Seasonal influenza vaccine without live virus is allowed.
• 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.
• Accompanying known active central nervous system (CNS) metastasis and/or cancerous meningitis.
• According to the standard of Common Adverse Event Terminology (CTCAE) 4th edition, peripheral neuropathy has been ≥2 grade.
• Severe hypersensitivity reactions to other monoclonal antibody treatments have occurred in the past.
• Accompanied by active autoimmune diseases, systemic treatment (ie, use of disease modifiers, corticosteroids or immunosuppressive drugs) is required within the past 2 years.
• 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.
• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Nivolumab; durvalumab; sintilimab; tislelizumab; camrelizumab; Platinum Compounds

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Inorganic Chemicals

Study Officials

• Xizhong Shen, MD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qi Chen, MD

CONTACT

86-17811921405; chenqimd@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 17, 2021
• Study Start: September 1, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: August 17, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 6 months and ending 5 years after the trial results were published.
• Access Criteria: All proposals requesting data access will need to specify how it is planned to use the data, and all proposals will need approval of all investigators before data release.

Locations

CN (1)