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

NCT07050940 | Recruiting

• 1 other identifier: Raffaello-Res
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Melanoma Metastatic

Keywords

melanoma stage IIIC or IV; untreated for metastatic disease

Outcome Measures

Primary Outcomes (1)

• Biological response rate

  proportion of responder patients at 12 weeks from treatment start. The response to treatment is based on the IHC level of HLA and NRLC5 at baseline and after 12 weeks from treatment start. An IHC level equal to 0 or 1+ is defined as low, while a IHC value equal to 2+ or 3+ is defined as high

  18 months

Secondary Outcomes (1)

• Objective Response Rate

  18 months

Study Arms (2)

Postbiotic+AntiPD1

EXPERIMENTAL

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

Dietary Supplement: Postbiotic; Drug: AntiPD1

AntiPD1

ACTIVE COMPARATOR

patient will be treated with AntiPD1 as per clinical standard practice

Drug: AntiPD1

Interventions

Postbiotic DIETARY_SUPPLEMENT

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

Postbiotic+AntiPD1

AntiPD1 DRUG

Antibody to PD1 approved for standard of care

AntiPD1; Postbiotic+AntiPD1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera di Perugia: lead
• Istituto Clinico Humanitas: collaborator

Study Sites (5)

Bari University-Oncologia medica

Bari, BA, Italy

NOT YET RECRUITING

Torino University-Le Molinette

Torino, TO, Italy

NOT YET RECRUITING

IRCCS Papa Giovanni II Bari

Bari, Italy

NOT YET RECRUITING

INT Milano

Milan, Italy

NOT YET RECRUITING

AO Perugia

Perugia, 06132, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 37738976 BACKGROUND

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mario Mandalà, MD

  AO perugia-University of perugia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mario Mandalà, MED

CONTACT

0039 0755784211; mario.mandala@unipg.it

Roberta Matocci, Pharmacist

CONTACT

00390755784099; roberta.matocci@ospedale.perugia.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: July 3, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5)