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

Leveraging Gut Microbiome and Immune System Dynamics During Immunotherapy to Develop Biomarkers of Response in Patients With Lung and Melanoma Cancer' and 'Intestinal Microbiota Profiling in Gynecologic Cancers to Identify Response-relevant Factors During Immune Checkpoint Blockade'

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Non Small Cell Lung Cancer; Endometrial Cancer; Melanoma (Skin Cancer)
• Intervention / Treatment: Biological: sample collection

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luigi Nezi, PhD; Phone Number: +39 02 94375171; Email: luigi.nezi@ieo.it
• Study Contact Backup: Name: Giulia Sedda, PhD; Email: giulia.sedda@ieo.it

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20141
      • Istituto Europeo di Oncologia
      • Principal Investigator: Gianluca Spitaleri, MD
      • Contact: Luigi Nezi, PhD; Phone Number: +39 02 94375171; Email: luigi.nezi@ieo.it
      • Contact: Giuli Sedda, PhD; Phone Number: +390294372178; Email: giulia.sedda@ieo.it
      • Principal Investigator: Monica Casiraghi, MD PhD
      • Principal Investigator: Giuseppe Caruso, MD PhD
      • Principal Investigator: Carolina Cimminiello, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

4.1 INCLUSION CRITERIA:

• 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.

Exclusion Criteria:

• 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
• Concomitant Medications/Vaccinations: medications or vaccinations specifically prohibited in the exclusion criteria are not allowed during the ongoing study. If there is a clinical indication for one of these or other medications or vaccinations specifically prohibited during the study that the investigator considers necessary for a subject's welfare, it will be administered at the discretion of the investigator in keeping with the community standards of medical care. All concomitant medication (within 28 days before the first dose) will be recorded on the case report form (CRF).
• 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
• Chemotherapy not specified in this protocol
• other Investigational agents
• Radiation therapy
• Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine.
• Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic aetiology. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
• Patients who, in the assessment by the investigator, require the use of any of the aforementioned treatments for clinical management should be removed from the study. Patients may receive other medications that the investigator deems to be medically necessary. The Exclusion Criteria describes other medications which are prohibited in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biological Sample collection; Biological Sample

Biological: sample collection; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endopoint	Correlation between Bacterial Antigens Mimicking-Tumor associated antigens (BAM-Ts) and clinical response to Immune Checkpoint Blockade (ICB).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoints	A. Correlation between circulating immunological factors during ICB and clinical response: Relapse-Free Survival (RFS) or Progression Free Survival (PFS), Overall Response Rate (ORR), Overall Survival (OS);	2 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoints	Correlation between, HLA allotypes and microbiota in correlation with clinical response RFS or PFS and OS;	5 year

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Luigi Nezi, PhD, Istituto Europeo di Oncologia; Principal Investigator: Monica Casiraghi, MD PhD, Istituto Europeo di Oncologia

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: July 24, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Genital Neoplasms, Female; Skin Diseases; Uterine Cervical Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Melanoma; Endometrial Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling
• Other Study ID Numbers: UID 4840; L2-614 (Other Identifier: Comitato Etico Lombardia 2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will insert all information into the paper.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No