Clinical trial NCT04477876: Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?
Official title: Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Melanoma
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inoperable stage III/ stage IV melanoma patients

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of effector cells activation and degranulation (CD69 and CD107a staining )
timeFrame: at inclusion
Secondary outcomes:
measure: Overall survival
timeFrame: at 1 year post inclusion
measure: Overall survival
timeFrame: at 2 years post inclusion
measure: Overall survival
timeFrame: at 3 years post inclusion
measure: Overall survival
timeFrame: at 4 years post inclusion
measure: Overall survival
timeFrame: at 5 years post inclusion
measure: Progression free survival
timeFrame: at 1 year
measure: Progression free survival
timeFrame: at 2 years
measure: Progression free survival
timeFrame: at 3 years
measure: Progression free survival
timeFrame: at 4 years
measure: Progression free survival
timeFrame: at 5 years
measure: Objective response rate
timeFrame: at one year
measure: Objective response rate
timeFrame: at 2 years
measure: Objective response rate
timeFrame: at 3 years
measure: Objective response rate
timeFrame: at 4 years
measure: Objective response rate
timeFrame: at 5 years
measure: Phenotypic characteristics of NK cells
timeFrame: at inclusion
measure: cytokine profile
timeFrame: at inclusion
measure: Détection and quantification of sCD160 in patients' serum
timeFrame: at inclusion
Other outcomes:
Locations:
Study officials:
References: