A Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma

NCT02434354 | Completed Phase 1 Results DMC

• 1 other identifier: UPCC 01615
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this trial is to evaluate the safety, tolerability and adverse event profile of pembrolizumab in subjects who have high risk melanoma before and after their standard of care surgical resection, and to collect tumor tissue from subjects before and after receipt of pembrolizumab to look at how the experimental drug interacts with tumor tissue. Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab

Conditions

Malignant Melanoma

Keywords

Clinical stage III or resectable stage IV melanoma (MEL)

Outcome Measures

Primary Outcomes (1)

• Number of Participants (%) With CTCAE Graded Adverse Events

  Safety as defined by 1) all grade 3/4 adverse events and 2) any grade adverse event that occurred in\>5% of patients. Toxicities are graded using CTCAE Version 4.

  within 30 days of final study treatment

Study Arms (1)

neo-adjuvant/adjuvant pembrolizaumab 200 mg IV

EXPERIMENTAL

All subjects will receive 1 cycle neo-adjuvant pembrolizumab 200mg IV followed by complete surgical resection followed by pembrolizumab Q3weeks for 1 year

Drug: pembrolizumab

Interventions

pembrolizumab DRUG

200 mg Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab

Also known as: keytruda

neo-adjuvant/adjuvant pembrolizaumab 200 mg IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must have clinical stage III or resectable stage IV MEL. Subject's may not have a diagnosis of uveal or mucosal melanoma.
• The subject must be expected to have an adequate amount of tumor burden to yield 2-4 pre-operative research core biopsy (14-gauge needle) specimens or the equivalent amount of tissue (4-6 mm punch biopsy), in addition, to the tissue required for diagnostic purposes.
• The subject must be expected to have an adequate amount of residual tumor after their pre-operative research tumor tissue collection, such that their operative research tumor collection will also yield at least 4-6 research core biopsy specimens or the equivalent amount of tissue
• The subject must be willing to undergo the two paired tumor tissue biopsy procedures to obtain samples for biomarker analysis. Tissue obtained must not be previously irradiated.
• Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
• The subject must be ≥ 18 years of age on day of signing informed consent.
• The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
• The subject must demonstrate adequate organ function as defined in Table 1, all screening labs must be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC)
• /mcL Platelets
• ,000/ mcL Hemoglobin
• g/dL or ≥5.6 mmol/L Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)
• ≤1.5 X upper limit of normal (ULN) OR
• mL/min for subject with creatinine levels \> 1.5 X institutional ULN UPCC# 01615: Tissue Collection Study of Pembrolizumab in Advanced Melanoma Version Date: 12/30/2014 Page 10 Hepatic Serum total bilirubin
• X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT)

You may not qualify if:

• Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
• Subject is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
• Subject has a known hypersensitivity to pembrolizumab or any of its ingredients.
• Subject has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
• Subject has had a prior monoclonal antibody 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.
• Subject has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents (including ipilimumab), interferon, high dose IL-1 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Subject has had prior chemotherapy, targeted small molecule therapy, 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
• For subject's who have received major surgery, the subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
• Subject has had radiation therapy to the tumor selected for research collection, or has had radiation therapy to any site within 4 weeks prior to study Day 1.
• Subject has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
• Subject has a known additional malignancy that is progressing or requires active treatment.
• Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Subjects with previously treated brain metastases will be eligible to participate provided they 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.
• Subject has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
• Note: Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019 Mar;25(3):454-461. doi: 10.1038/s41591-019-0357-y. Epub 2019 Feb 25.

  PMID: 30804515 RESULT

• Sharon CE, Tortorello GN, Ma KL, Huang AC, Xu X, Giles LR, McGettigan S, Kreider K, Schuchter LM, Mathew AJ, Amaravadi RK, Gimotty PA, Miura JT, Karakousis GC, Mitchell TC. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol. 2023 Sep;34(9):806-812. doi: 10.1016/j.annonc.2023.06.006. Epub 2023 Jul 4.

  PMID: 37414215 DERIVED

Related Links

• Pubmed link

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. Tara Mitchell
• Organization: Abramson Cancer Center

tara.mitchell@pennmedicine.upenn.edu

215-662-7908

Study Officials

• Tara Mitchell, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: May 5, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2019
• Study Completion: September 29, 2021
• Last Updated: June 16, 2022
• Results First Posted: January 5, 2021

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)