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Study of the Effects of Pembrolizumab in Patients With Advanced Solid Tumors (INSPIRE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02644369
Recruitment Status : Active, not recruiting
First Posted : December 31, 2015
Last Update Posted : January 10, 2023
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

This is a phase 2 study whose main purpose is to evaluate gene changes and immune biomarkers in patients with solid tumors during treatment with pembrolizumab and in relation to response to treatment.

Pembrolizumab is a monoclonal antibody that is designed to block a protein called programmed cell death 1 ligand 1 (PD-L1) which will allow the body's immune system to kill the cancer cells.

Condition or disease Intervention/treatment Phase
Squamous Cell Cancer of Head and Neck Triple Negative Breast Cancer Epithelial Ovarian Cancer Malignant Melanoma Advanced Solid Tumors Biological: Pembrolizumab Phase 2

Detailed Description:
This study will involve treatment with pembrolizumab, tests and procedures done for safety, and the collection of archival tumor tissue, fresh tumor biopsies, and blood samples for biomarker research (including genetic testing).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigator-initiated Phase II Study of Pembrolizumab Immunological Response Evaluation
Actual Study Start Date : March 21, 2016
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Pembrolizumab
Pembrolizumab will be given by intravenous infusion (IV, given by vein) at a dose of 200 mg, once every 3 weeks.
Biological: Pembrolizumab
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Other Names:
  • Keytruda(TM)
  • MK-3475

Primary Outcome Measures :
  1. Changes in genomic and immune biomarkers that will be measured in blood and tumor pre-treatment, on-treatment and at progression (progression biopsies only done for those who have complete or partial responses, or stable disease for more than 4 months) [ Time Frame: 5 years ]
    T-test or Wilcoxon's test

Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 5 years ]
  2. Changes in circulating tumor DNA genomic biomarkers [ Time Frame: 5 years ]
  3. Changes in radiomic imaging parameters [ Time Frame: 5 years ]
  4. Correlation between tumor genomic profiles and radiomic imaging signatures [ Time Frame: 5 years ]
  5. Changes in immune cell subsets in the blood and tumor microenvironment [ Time Frame: 5 years ]
  6. Positive predictive value and negative predictive value of in vitro predictive assay for Pembrolizumab response [ Time Frame: 5 years ]
  7. Distribution of drug tumor penetration using a mass spectrometry assay [ Time Frame: 5 years ]
  8. Baseline tumor RNA expression profile for immune inhibitory genes [ Time Frame: 5 years ]
  9. Comparison of baseline tumor RNA expression profile for immune inhibitory genes with clinical outcome (response) [ Time Frame: 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be 18 years of age or older on day of signing informed consent.
  • Have histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens.
  • Have one of the following advanced (unresectable and/or metastatic) solid tumor indications:

    • Squamous cell cancer of head and neck
    • Triple negative breast cancer
    • Epithelial ovarian cancer
    • Malignant melanoma
    • Advanced solid tumors
  • Have measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient safety concern) will not be eligible for this study.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function.
  • Negative pregnancy test for female patients of childbearing potential.
  • Must use approved methods of birth control during the course of the study and for 120 days after the last dose of study drug.

Exclusion Criteria:

  • 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 of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial 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) within 4 weeks prior to study Day 1 or who has not recovered 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 from adverse events due to a previously administered agent.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years
  • Has known history of, or any evidence of active, non-infectious 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 patient's participation for the full duration of the trial, or is not in the best interest of the patient 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.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with 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.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02644369

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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Merck Sharp & Dohme LLC
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Principal Investigator: Lillian Siu, M.D. Princess Margaret Cancer Centre
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02644369    
Other Study ID Numbers: INSPIRE-001
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: January 10, 2023
Last Verified: December 2022
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Carcinoma, Ovarian Epithelial
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Genital Diseases
Endocrine System Diseases
Gonadal Disorders
Breast Neoplasms
Breast Diseases
Skin Diseases