Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?

Melanoma Clinical Trial

— NKCD160MEL  

Official title:

Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04477876
• Other study ID #: APHP190953
• Status: Not yet recruiting
• Start date: September 1, 2020
• Est. completion date: December 15, 2027

Study information

• Verified date: February 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Celeste Lebbe, Pr
• Phone: 01 42 49 99 61
• Email: celeste.lebbe[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Although immunotherapy revolutionized melanoma outcomes over the last 10 years, only 40-50% of patients respond to treatments and 25% develop acquired resistances. Natural Killer (NK) cells naturally recognize and kill tumor cells. However, the immunosuppressive micro-environment generated by the tumor decreases NK cells' killing activity. CD160 is a NK cell receptor identified and characterized in our laboratory. Engagement of the GPI isoform (CD160-GPI) initiates NK cell cytotoxic response. Upon NK cell activation, a transmembrane isoform (CD160-TM) is neo-synthesized which promotes the amplification of activated NK cell cytotoxicity.

The aim of this study is to assess the phenotypic profile of advanced stages melanoma patients' NK cells (mainly CD160-TM expression or its induction) and therefore the therapeutic potential of the use of an anti-CD160-TM agonist antibody to boost the NK-dependent mechanism leading to tumor depletion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: December 15, 2027
• Est. primary completion date: December 15, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria :

• Patients aged18-years old or over

• ECOG score between 0-2

• Inoperable stage III or stage IV melanoma

• Naïve of treatment or in progression after one or several treatment lines

• Give their written consent for the present study and be included in MelBase cohort.

• health insurance coverage.

Supplementary inclusion criteria for part II :

• skin or subcutaneous melanoma lesions

• agree and inform consent for a cutaneous biopsy or a tumor sample if presenting lymph nodes involvement if part of the usual clinical practice.

Exclusion Criteria:

• Pregnant and breastfeeding women

• Patients with psychiatric disorders

• Patients already included in another clinical trial

• Having received chemotherapy or radiotherapy during the last 4 weeks,

• Patient presenting another solid or blood cancer, chronic viral infection (e.g. HIV, HBV or HCV)

• Been treated with more than 10mg of steroids until the 4 weeks before inclusion.

• Refusal to participate to the study

• Patients under guardianship or curatorship

• Patients on state medical aid

Related Conditions & MeSH terms

• Melanoma

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of effector cells activation and degranulation (CD69 and CD107a staining )	Difference between cells incubated with the anti CD160-TM antibody and with isotipic control ab ( flow cytometry)	at inclusion
Secondary	Overall survival		at 1 year post inclusion
Secondary	Overall survival		at 2 years post inclusion
Secondary	Overall survival		at 3 years post inclusion
Secondary	Overall survival		at 4 years post inclusion
Secondary	Overall survival		at 5 years post inclusion
Secondary	Progression free survival		at 1 year
Secondary	Progression free survival		at 2 years
Secondary	Progression free survival		at 3 years
Secondary	Progression free survival		at 4 years
Secondary	Progression free survival		at 5 years
Secondary	Objective response rate		at one year
Secondary	Objective response rate		at 2 years
Secondary	Objective response rate		at 3 years
Secondary	Objective response rate		at 4 years
Secondary	Objective response rate		at 5 years
Secondary	Phenotypic characteristics of NK cells	Assessment by flow cytometry of the expression levels of activating or inhibitory receptors (e.g. CD160-GPI, NKp46), phenotypic markers (e.g CD16, CD3), as well as activation (CD69) and degranulation (CD107a) markers by the NK cell population (defined as CD3- CD56+ cell). Results will be expressed as the % of positive cells for each marker among the NK cell population	at inclusion
Secondary	cytokine profile	Assessment by flow cytometry using a cytokine beads array (BD Biosciences) of the Th1/Th2/Th17 cytokine content. The presence of the following cytokine will be assessed: IL17-A, IFN-g, TNF, IL10, IL-6, IL-4 and IL-2. The mean fluorescence intensities will be recorded and quantifications will be done, using an individual standard curve, for each cytokine. Results will be expressed in pg/ml.	at inclusion
Secondary	Détection and quantification of sCD160 in patients' serum		at inclusion