Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Recruiting

• Conditions: Melanoma; Breast Cancer; Squamous Cell Carcinoma of Head and Neck; NSCLC; Urinary Bladder Cancer; Renal Cell Carcinoma; Small Cell Carcinoma
• Interventions: Other: MDSC quantification

• Registration Number: NCT05621837
• Lead Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary

The Serpentine (Stratify cancER PatiENTs by ImmuNosupprEssion) project, represents the most consistent effort so far attempted to translate MDSC into clinical practise by producing an off-the-shelf compliant assay for quantifying these cells in peripheral blood.

Detailed Description

The study will demonstrate that this assay helps personalizing cancer therapies by tailoring them to immune patient features. The project will also take advantage of innovative and high-throughput techniques to define additional MDSC related biomarkers and, most importantly, to identify novel drugs for Myeloid-derived Suppressor Cells (MDSC) blocking in predisposed patients. Finally,it will perform the first survey assessing the link between MDSC and "perceived social isolation", an emerging western social problem recently shown to cause myeloid cell dysfunction and immunosuppression though neuroendocrine circuits. Globally, the Serpentine proposal has the ambitious goal to translate into the clinical oncological practise the use of MDSC quantification as a tool for the systematic assessment of systemic immunosuppression, providing at the same time operational insights into the strategies to overcome this pillar mechanism of cancer progression.

Study Timeline

• Study Start: 2022-03-10
• Study First Submitted: 2022-10-03
• Study First Submitted QC: 2022-11-11
• Study First Posted: 2022-11-18
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Age and gender-matched healthy donors	MDSC quantification	Age and gender-matched healthy donors (n=400) will be enrolled in the study, to allow us investigating the same immunological parameters under physiological conditions and define normal values for the myeloid-related biomarkers here assessed.
Advanced RCC(renal cell carcinoma) patients	MDSC quantification	MDSC quantification Advanced RCC patients receiving immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4, or combinations) or anti-angiogenics alone or combined with immune checkpoint inhibitors; locally advanced/metastatic UC(Urothelial Carcinoma) patients receiving first-line chemotherapy, immune checkpoint inhibitors or combinations (n=100);
Metastatic melanoma patients	MDSC quantification	MDSC quantification in Metastatic melanoma patients undergoing first/second-line treatment with BRAF and MEK inhibitors (BRAFi+MEKi) or immune checkpoint inhibitors (antagonists of PD-1 or CTL4, or both) (n=100);
hormone receptor positive/Human Epidermal growth factor Receptor-2 negative cancer patients	MDSC quantification	MDSC quantification in Metastatic HR+(hormone receptor positive)/ HER2-(Human Epidermal growth factor Receptor-2 negative) breast cancer patients already treated with a combination of an hormonal agent and a CDK(Cyclin-dependent kinase)4/6 inhibitor and receiving chemotherapy (n=100);
SCCHN or SCC(Small Cell Carcinoma) patients	MDSC quantification	MDSC quantification in SCCHN or SCC(Small Cell Carcinoma) patients treated with first-line chemotherapy, cetuximab,immune checkpoint inhibitors or combinations (n=100).
NSCLC patients	MDSC quantification	MDSC quantification in NSCLC patients undergoing radical surgery for stage III cancer (n=100);patients with unresectable/metastatic NSCLC receiving first line treatment with chemotherapy, immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4) or combinations (n=100).

Primary Outcome Measures

Name	Time	Method
Clinical endpoint_PFS	Through study completion, an average of 2 year	Progression-Free Survival (PFS)
Clinical endpoint_OS	Through study completion, an average of 2 year	Overall Survival (OS)
Immunological endpoint	Through study completion, an average of 2 year	Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC
Clinical endpoint_ORR	Through study completion, an average of 2 year	Overall Response Rate (ORR)

Secondary Outcome Measures

Name	Time	Method
Transcriptional signatures_myeloid cells	baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)	Transcriptional signatures identified on sorted myeloid cells form whole blood
Transcriptional signatures_PBMC	baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)	Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood
Phospho-kinome signature result	Through study completion, an average of 2 year	Phospho-kinome signature as assessed by Cytof analysis in stored PBMC
Socio-Economical-Psychological (SEP) score	Through study completion, an average of 2 year	Socioeconomic and psychological (perceived social isolation) score, calculated through a dedicated questionnaire
Myeloid Index Score (MIS)	Through study completion, an average of 2 year	Myeloid Index Score (MIS)=0 vs MIS\>0 or higher values
Index score values	Through study completion, an average of 2 year	Index score values on plasma cytokine concentration or MDSC-miRs
Metabolomic profiles	Through study completion, an average of 2 year	The concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism

Trial Locations

Locations (1)

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy