Gut Microbiome in Patients With Lung and Melanoma Cancer and Intestinal Microbiota in Gynecologic Cancers

NCT07815873 | Not Yet Recruiting

• 2 other identifiers: UID 4840L2-614
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the role of the gut microbiota and its derived factors, including bacterial-associated antigens that mimic tumor-associated antigens, in predicting response to immune checkpoint inhibitor immunotherapies in patients with various types of cancer. The aim is to explore whether gut microbiota-mediated immunological modulation is specific to the tumor being treated and whether it can be used to enhance antitumor response.

Conditions

Non Small Cell Lung Cancer; Melanoma (Skin Cancer); Endometrial Cancer; Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Primary Endopoint

  Correlation between Bacterial Antigens Mimicking-Tumor associated antigens (BAM-Ts) and clinical response to Immune Checkpoint Blockade (ICB).

  1 year

Secondary Outcomes (1)

• Secondary Endpoints

  2 year

Other Outcomes (1)

• Exploratory Endpoints

  5 year

Study Arms (1)

Biological Sample collection

EXPERIMENTAL

Biological Sample

Biological: sample collection

Interventions

sample collection BIOLOGICAL

Clinical and radiological assessment will be performed at the enrollment and every 3 +/- 1 months. Clinical information and biological samples will be collected also at 2 years from surgery or start of therapy. We plan collection of a maximum of 13 faecal and blood samples per patient (1 baseline + a maximum of 11 during treatment ± 1 disease progression, ± 10%). In addition, we expect to collect fresh stools and tissue biopsies from at least 3-5 patients per group every year, which will be dedicated to our translational studies.

Biological Sample collection

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed disease (see 3.1)
• (i) patients with local advanced or metastatic NSCLC candidate to first-line ICB monotherapy or chemo-ICB combination OR (ii) patients with cutaneous melanoma candidate to first-line or adjuvant ICB (iii) patients with primary advanced or first recurrence endometrial or cervical cancer candidate to chemo-ICB combination
• Signed Written Informed Consent
• Males and Females, ages ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Have evaluable disease based on i-RECIST 1.1
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and all protocol procedures.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion, whenever possible.
• Known mutation/molecular status as determined by local institutional standard (NSCLC: available comprehensive molecular analysis, melanoma: PD-L1 TPS score, BRAF V600, EC: p53, POLE, MMR status, CC: PD-L1 CPS score. Both wild type and mutation positive are eligible. Regarding gynecologic cancers, EC patients will be eligible for the study regardless of the MMR status (MMRd or MMRp), while only CC patients with a PD-L1 combined positive score (CPS) ≥1 will be eligible.
• Patients who have been previously treated in the adjuvant setting for melanoma will be eligible for treatment after a 28-day washout period.
• Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team.
• Demonstrate adequate organ function as defined below: Hematologic Absolute neutrophil count (ANC) \>/= 1.5 X 10\^9/L; Hemoglobin \>/= 9.5 g/dL Platelets \>/= 100 X 10\^9/L PT/INR and PTT \</= 1.5 X ULN. Hepatic Total bilirubin \</= 1.5 X ULN (isolated bilirubin \>1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) AST and ALT Albumin \</= 2.5 X ULN 1 \>/=2.5 g/dL Renal Creatinine OR Calculated creatinine clearance OR 24-hour urine creatinine clearance \</=1.5 X ULN 2 \>/= 50 mL/min \>/= 50 mL/min.
• The individual methods of contraception and duration should be determined in consultation with the investigator.
• Women must not be breastfeeding.

You may not qualify if:

• Previous chemotherapy (\< 28 days washout), radiation therapy, immunotherapy, or biologic therapy
• Any major surgery within the last 3 weeks
• Pregnant or lactating female
• Unwillingness or inability to follow the procedures
• Grade 3 and 4 adverse event conditioning ICB interruption
• Known oncogene-addicted NSCLC, with the exception of KRAS G12C and BRAF V600E mutant NSCLC Any serious or uncontrolled medical disorder
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation).
• Patients with active, known or suspected autoimmune disease such as Inflammatory Bowel Disease, Lupus, etc. or other conditions requiring systemic corticosteroids or other systemic immunosuppressive medications.
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
• Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody.
• Antibiotic or antimycotic medications within 45 days from the beginning of ICB
• Positive test result for hepatitis B or C virus
• Human immunodeficiency virus or known acquired immunodeficiency syndrome
• Patients are prohibited from receiving the following therapies during the Screening and Treatment Phase (including retreatment for post-complete response relapse) of this study:
• Immunotherapy not specified in this protocol

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

Istituto europeo di oncologia

Milan, MI, 20141, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Endometrial Neoplasms; Uterine Cervical Neoplasms

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Cervical Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Luigi Nezi, PhD

  Istituto Europeo di Oncologia

  PRINCIPAL INVESTIGATOR

• Monica Casiraghi, MD PhD

  Istituto Europeo di Oncologia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luigi Nezi, PhD

CONTACT

+39 02 94375171; luigi.nezi@ieo.it

Giulia Sedda, PhD

CONTACT

giulia.sedda@ieo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: September 11, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2031
• Last Updated: September 11, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)