Melanoma MetastaticNCT07050940
Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma Study
A study testing Postbiotic and AntiPD1 in people with Melanoma Metastatic, run by Azienda Ospedaliera di Perugia at 5 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Metastatic
- What is being tested?
- Postbiotic and AntiPD1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 5 sitesItaly
- Study dates
- 1 Feb 2025to 1 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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 has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, residual toxicity no worse than Grade 1 [Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met]).
- 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
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Italy5 sites, 5 recruiting
- Not yet recruiting
Bari University-Oncologia medica
Bari, BA
Marco Tucci, MD, 00393452646152, marco.tucci@uniba.it
- Not yet recruiting
IRCCS Papa Giovanni II Bari
Bari
Michele Guida, MD, 00390805555255, micguida57@gmail.com
- Not yet recruiting
INT Milano
Milan
Alice Indini, MD, 00390223902844, alice.indini@gmail.com
- Recruiting
AO Perugia
Perugia, 06132
Mario Mandala, MD, 00390755784211, mario.mandala@unipg.it
- Not yet recruiting
Torino University-Le Molinette
Torino, TO
Pietro Quaglino, MD, 00393355718889, pietro.quaglino@unito.it
About this study
Official title: Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma: a Phase II Randomized Study With Correlative Biomarkers' Analysis:
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.
Read the 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
- Being tested
- Postbiotic, AntiPD1
- Keywords
- melanoma stage IIIC or IV, untreated for metastatic disease
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PostbioticDietary supplement
postbiotic food supplement PostbiotiX-HLA 1 capsule (200mg) /day
AntiPD1Drug
Antibody to PD1 approved for standard of care
| Study group | Role | What they receive |
|---|---|---|
| Postbiotic+AntiPD1 | Experimental | patient will be treated with the postbiotic agent and AntiPD1 choose as for standard practice Receives: Dietary Supplement: Postbiotic; Drug: AntiPD1 |
| AntiPD1 | Active comparator | patient will be treated with AntiPD1 as per clinical standard practice Receives: Drug: AntiPD1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months
Secondary outcomes (1)
Objective Response Rate
the proportion of patients with a complete (CR) or partial response (PR) as best response during treatment as determined by RECIST 1.1.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2025
- Study start1 Feb 2025
- Primary completion1 Aug 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera di Perugia
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto Clinico Humanitas
- Responsible party
- Principal investigator, Mario Mandalà, Azienda Ospedaliera di Perugia
- Investigators
- Mario Mandalà, MD, Principal investigator, AO perugia-University of perugia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07050940
- Sponsor's protocol ID
- Raffaello-Res
- Status last verified
- Jul 2025
- First submitted
- 24 Mar 2025
- Last updated
- 3 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: only for patient referral to italian site
Publications
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.
PubMed 37738976
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma: a Phase II Randomized Study With Correlative Biomarkers' Analysis:
- ClinicalTrials.gov ID
- NCT07050940
- Acronym / sponsor ID
- Raffaello-Res
- Conditions
- Melanoma Metastatic
- Keywords
- melanoma stage IIIC or IV, untreated for metastatic disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Azienda Ospedaliera di PerugiaUniversity, hospital or other
- Collaborators
- Istituto Clinico Humanitas
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- 1 Aug 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 3 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Postbiotic+AntiPD1 | Experimental | Dietary Supplement: Postbiotic, Drug: AntiPD1patient will be treated with the postbiotic agent and AntiPD1 choose as for standard practice |
| AntiPD1 | Active comparator | Drug: AntiPD1patient will be treated with AntiPD1 as per clinical standard practice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Postbioticpostbiotic food supplement PostbiotiX-HLA 1 capsule (200mg) /day | Dietary supplement | Postbiotic+AntiPD1 |
| AntiPD1Antibody to PD1 approved for standard of care | Drug | AntiPD1, Postbiotic+AntiPD1 |
Primary outcome
Biological response rate
Time frame: 18 months
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
1 secondary outcome
Objective Response Rate
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Results publication: PubMed 37738976Ferrari 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.
- Individual participant dataSharing planned: No. only for patient referral to italian site
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Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mario Mandalà, MD principal investigator
AO perugia-University of perugia
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Postbiotic and AntiPD1 in people with Melanoma Metastatic, run by Azienda Ospedaliera di Perugia at 5 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mario Mandalà, MED (0039 0755784211, mario.mandala@unipg.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biological response rate (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07050940, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.