Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma Study

NCT ID: NCT07050940

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2026-08-01

Brief Summary

The association between microbiota and response to ICI-based therapy reflects the ability of bacterial metabolites to upregulate MHC class I APM component expression and/or function in cancer cells, leading to their elimination by the host's immune system.

Thus, the aim of this project is to evaluate the ability of anti PD-1 combined with postbiotic, that here will be a coadjuvant of a standard immunotherapy to upregulate MHC class I APM component expression and/or function in cancer cells compared to anti PD-1 alone in first line advanced melanoma patients.

Detailed Description

The study is designed for the primary endpoint as a non-comparative calibrated phase II clinical trial. Patients assigned to the anti PD-1 alone arm will be considered as the calibration group. . Results obtained in the calibration arm will be used to judge the results obtained in the experimental arm.

This is a study protocol settled up on a biological primary endpoint To evaluate the activity of the combination of anti PD-1 plus postbiotic in terms of upregulation of MHC class I APM component expression and/or function in advanced, treatment naïve, cutaneous melanoma patients. The Clinical Objectives is to evaluate the activity of the combination of anti PD-1 plus postbiotic compared to anti PD-1 alone in terms of overall response rate (ORR).

To evaluate the efficacy of the combination of anti PD-1 plus postbiotic compared to anti PD-1 alone in terms of PFS.

Conditions

Melanoma Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Postbiotic+AntiPD1

patient will be treated with the postbiotic agent and AntiPD1 choose as for standard practice

Group Type: EXPERIMENTAL

Postbiotic

Intervention Type: DIETARY_SUPPLEMENT

postbiotic food supplement PostbiotiX-HLA 1 capsule (200mg) /day

AntiPD1

Intervention Type: DRUG

Antibody to PD1 approved for standard of care

AntiPD1

patient will be treated with AntiPD1 as per clinical standard practice

Group Type: ACTIVE_COMPARATOR

AntiPD1

Intervention Type: DRUG

Antibody to PD1 approved for standard of care

Interventions

Postbiotic

postbiotic food supplement PostbiotiX-HLA 1 capsule (200mg) /day

Intervention Type: DIETARY_SUPPLEMENT

AntiPD1

Antibody to PD1 approved for standard of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients 18 years or older
• Histologically confirmed, unresectable stage IIIC or IV metastatic melanoma;
• Eastern Cooperative Oncology Group performance status of 0 or 1;
• The patient must treatment naïve for metastatic disease
• Patients who have received anti-PD-1 therapy or anti BRAF/MEK in adjuvant setting and relapsed after 6 months of ending adjuvant therapy are allowed to enter clinical study.
• Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. To qualify, archival tissue must have been sampled after last exposure to any systemic anti-neoplastic agent (including TVEC or anti-PD-L1 therapy whichever is last). Patients unable to undergo a biopsy may be enrolled if risk/benefit ratio of biopsy is considered unfavorable and/or when a biopsy would likely lead to significant delays in care. This decision must be accompanied by supporting documentation from the Investigator and performed in consultation with Medical Monitor. All pretreatment tissue must have been collected no more than 120 days prior to screening.
• Patient who has received prior systemic anti-neoplastic agent(s) must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study, or 4 weeks if the half-life of a given investigational agent is not known.
• Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 5 days before the first dose of study drug and an estimated life expectancy of at least 3 months.
• Patient has adequate hematologic reserve as evidenced by:

Absolute neutrophil count (ANC) of ≥1000/μL, Absolute lymphocyte count of

≥500/μL, Platelet count of ≥75,000/μL, and Hemoglobin of ≥9 g/dL (patients may be transfused to this level, if necessary, but transfusion must occur >1 week prior to the first dose of study drug).

• Patient has adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values ≤3 × the upper limit of normal (ULN) and serum total bilirubin values of ≤1.5 × ULN (≤2 × ULN for patients with known Gilbert's syndrome) for the reference laboratory measured within 7 days prior to the first dose of study drug. For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase and 2 × ULN for bilirubin.
• Patient has adequate renal function as evidenced by a serum creatinine ≤1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of ≥45 mL/min by the Cockcroft-Gault Equation measured within 7 days prior to the first dose of study drug.
• Patient has international normalized ratio (INR) AND/OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case INR and/or PT and aPTT must be within the desired therapeutic range of intended use for such anticoagulants.
• Patient agrees to abide by the contraceptive requirements detailed in the protocol.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within 3 days before the first dose of study drug (see the protocol for the definition of WOCBP).
• Life expectancy more than 3 months
• Presence of instrumentally or clinically measurable or evaluable lesions Informed consent obtained

Exclusion Criteria

• Patients with mucosal or with a primary ocular melanoma
• Active symptomatic or asymptomatic brain metastases
• Patients with the following disorders: active, known, or suspected autoimmune disease (except for some non-serious disorders, such as vitiligo and type 1 diabetes mellitus, as specified in the study protocol);
• Previous malignancies (exceptions skin basocellular or squamocellular carcinoma radically resected, in situ uterine cervix in situ carcinoma radically resected) in the previous 2 years.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Clinico Humanitas

OTHER

Sponsor Role: collaborator

Azienda Ospedaliera di Perugia

OTHER

Sponsor Role: lead

Responsible Party

Mario Mandalà

Director of Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mario Mandalà, MD

Role: PRINCIPAL_INVESTIGATOR

AO perugia-University of perugia

Locations

Bari University-Oncologia medica

Bari, BA, Italy

Site Status: NOT_YET_RECRUITING

Torino University-Le Molinette

Torino, TO, Italy

Site Status: NOT_YET_RECRUITING

IRCCS Papa Giovanni II Bari

Bari, , Italy

Site Status: NOT_YET_RECRUITING

INT Milano

Milan, , Italy

Site Status: NOT_YET_RECRUITING

AO Perugia

Perugia, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Mario Mandalà, MED

Role: CONTACT

mario.mandala@unipg.it

0039 0755784211

Roberta Matocci, Pharmacist

Role: CONTACT

roberta.matocci@ospedale.perugia.it

00390755784099

Facility Contacts

Marco Tucci, MD

Role: primary

marco.tucci@uniba.it

00393452646152

Pietro Quaglino, MD

Role: primary

pietro.quaglino@unito.it

00393355718889

Michele Guida, MD

Role: primary

micguida57@gmail.com

00390805555255

Alice Indini, MD

Role: primary

alice.indini@gmail.com

00390223902844

Mario Mandala, MD

Role: primary

mario.mandala@unipg.it

00390755784211

References

Ferrari V, Lo Cascio A, Melacarne A, Tanaskovic N, Mozzarelli AM, Tiraboschi L, Lizier M, Salvi M, Braga D, Algieri F, Penna G, Rescigno M. Sensitizing cancer cells to immune checkpoint inhibitors by microbiota-mediated upregulation of HLA class I. Cancer Cell. 2023 Oct 9;41(10):1717-1730.e4. doi: 10.1016/j.ccell.2023.08.014. Epub 2023 Sep 21.

Reference Type: BACKGROUND

PMID: 37738976 (View on PubMed)

Other Identifiers

Raffaello-Res

Identifier Type: -

Identifier Source: org_study_id