Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target? (NKCD160MEL)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma

• Study Type: Observational
• Enrollment (Anticipated): 55

Contacts and Locations

• Study Contact: Name: Celeste Lebbe, Pr; Phone Number: 01 42 49 99 61; Email: celeste.lebbe@aphp.fr
• Study Contact Backup: Name: Matthieu Resche-Rigon, Pr; Phone Number: +3342499742; Email: matthieu.resche-rigon@univ-paris-diderot.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Inoperable stage III/ stage IV melanoma patients

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate		at 4 years
Overall survival		at 1 year post inclusion
Overall survival		at 2 years post inclusion
Overall survival		at 3 years post inclusion
Overall survival		at 4 years post inclusion
Overall survival		at 5 years post inclusion
Progression free survival		at 1 year
Progression free survival		at 2 years
Progression free survival		at 3 years
Progression free survival		at 4 years
Progression free survival		at 5 years
Objective response rate		at one year
Objective response rate		at 2 years
Objective response rate		at 3 years
Objective response rate		at 5 years
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
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
Détection and quantification of sCD160 in patients' serum		at inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): December 15, 2027
• Study Completion (Anticipated): December 15, 2027

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: APHP190953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No