Quantifying Systemic Immunosuppression to Personalize Cancer Therapy (Serpentine)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status: Enrolling

Conditions: Urinary Bladder Cancer; Breast Cancer; Melanoma; Squamous Cell Carcinoma of Head and Neck; Small Cell Carcinoma; Renal Cell Carcinoma; NSCLC

Treatments: Other: MDSC quantification

Study type: Observational

Funder types: Other

Identifiers

NCT05621837

INT 48/21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Histologically documented diagnosis of metastatic/locally advanced melanoma, hormone-refractory breast cancer, RCC and UC, SCCHN, SCC or NSCLC, stage III resectable NSCLC will also be included
• Will and ability to comply with the protocol
• Willingness and ability to provide an adequate archival Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample available for exploratory biomarker analysis
• Age from 18 to 90 years at the time of recruitment
• ECOG Performance Status <= 2
• Understanding and signature of the informed consent
• Consenting to participate to the socio-economical-psychological survey

Exclusion Criteria

• Known history of HIV infection
• Serious neurological or psychiatric disorders
• Pregnancy or lactation
• Inability or unwillingness of participant to give written informed consent
• Inability or unwillingness to be regularly followed up at the same center

Trial design

1,000 participants in 6 patient groups

Metastatic melanoma patients

Description:

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);

Treatment:

Other: MDSC quantification

hormone receptor positive/Human Epidermal growth factor Receptor-2 negative cancer patients

Description:

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);

Treatment:

Other: MDSC quantification

Advanced RCC(renal cell carcinoma) patients

Description:

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);

Treatment:

Other: MDSC quantification

SCCHN or SCC(Small Cell Carcinoma) patients

Description:

MDSC quantification in SCCHN or SCC(Small Cell Carcinoma) patients treated with first-line chemotherapy, cetuximab,immune checkpoint inhibitors or combinations (n=100).

Treatment:

Other: MDSC quantification

NSCLC patients

Description:

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).

Treatment:

Other: MDSC quantification

Age and gender-matched healthy donors

Description:

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.

Treatment:

Other: MDSC quantification