Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nina Bhardwaj, MD, PhD

Melanoma is an immune-modulated malignancy and immune checkpoint modulators which inhibit PD-1 function (pembrolizumab, nivolumab) have demonstrated clinical efficacy as treatment for patients with stage IV melanoma. Pembrolizumab across a range of doses in phase I investigation has demonstrated clinical efficacy with RR approximately 27%. By better understanding how NK cell function and exhaustion interplays with PD1 function and activity, potentially more efficacious combination therapies can be developed. The pharmacodynamic studies to be performed as part of this trial will provide such information.

Pembrolizumab Effects on NK Cell Exhaustion in Melanoma (Merck NK-IIT)

A Phase II Study Assessing the Effect of Pembrolizumab Induced Changes to the NK Cell Exhaustion Phenotype on the Efficacy of PD-1 Targeted Treatment in Patients With Unresectable Stage III or Stage IV Melanoma

NK cell exhaustion will be assess by flow cytometry and expressed as % of LAMP-1 positive cells.

IFN gamma will be assess by flow cytometry and then expressed as % of positive cell for IFN gamma.

NK proliferation will be assess by flow cytometry and then expressed as percentage of proliferating cells.

MICA plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.

HMGB-1 plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.

CEACAM-1 expression will be assessed by flow cytometry and express as % of positive NK cells for CEACAM-1

One year survival following pembrolizumab treatment in patients with Unresectable stage III or IV melanoma using Immune-Related Response Criteria.

Progression free survival in pembrolizumab treated patients with unresectable stage III or IV melanoma using Immune-Related Response Criteria.

Nina Bhardwaj

Professor

there was only one person in this study. No participants in Healthy Control arm.

200 mg IV infusion every 3 weeks

Pembrolizumab: Day 1 of each 3 week cycle

Healthy Control

60-69 years

70-79 years

80-89 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Nina Bhardwaj

Healthy Donors

Percent of LAMP-1 Positive Cells

Percent of Positive Cell for IFN Gamma

Percent of Proliferating Cells

MICA Plasma Level

HMGB-1 Plasma Level

% of Positive NK Cells for CEACAM-1

Incidence of Overall Survival

Progression Free Survival (PFS) Rate

Overall Study

Spots Global Cancer Trial Database for nk cell exhaustion