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

NCT03241927 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 16-2526
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

Pembrolizumab; NK Cell Exhaustion; PD-1; Unresectable; Stage III; Stage IV

Outcome Measures

Primary Outcomes (3)

• Percent of LAMP-1 Positive Cells

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

  up to 3 years

• Percent of Positive Cell for IFN Gamma

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

  up to 3 years

• Percent of Proliferating Cells

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

  up to 3 years

Secondary Outcomes (5)

• MICA Plasma Level

  up to 104 levels

• HMGB-1 Plasma Level

  up to 104 weeks

• % of Positive NK Cells for CEACAM-1

  up to 104 weeks

• Incidence of Overall Survival

  1 year

• Progression Free Survival (PFS) Rate

  6 months

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

200 mg IV infusion every 3 weeks

Biological: Pembrolizumab

Healthy Donors

NO INTERVENTION

Interventions

Pembrolizumab BIOLOGICAL

Day 1 of each 3 week cycle

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Have Unresectable stage III or stage IV melanoma
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1 and be able to be followed over time by Immune related response criteria (irRC) for treatment decisions.
• Have a performance status of 0, 1, or 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.6.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) treatment within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, the subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided the subjects are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• If pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• Nina Bhardwaj: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Nina Bhardwaj
• Organization: Icahn School of Medicine at Mount Sinai

nina.bhardwaj@mssm.edu

212-824-8427

Study Officials

• Nina Bhardwaj, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 8, 2017
• Study Start: December 20, 2017
• Primary Completion: June 6, 2018
• Study Completion: June 6, 2018
• Last Updated: November 23, 2020
• Results First Posted: November 23, 2020

Record last verified: 2020-10

Locations

US (1)