Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/KEYNOTE-001)

Overview

  • Study type

    Interventional
  • Study phase

    I
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 11-000252
    • Jacksonville, Florida: 11-000252
    • Rochester, Minnesota: 11-000252
    NCT ID: NCT01295827
    Sponsor Protocol Number: MK-3475-001

About this study

This study will be done in 6 parts. In Part A the dose of intravenous (IV) pembrolizumab (MK-3475) will be escalated to find the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically or cytologically confirmed diagnosis of any type of carcinoma or melanoma (MEL). Part B of the study will explore the safety, tolerability, and efficacy of the drug in participants with advanced or metastatic MEL and compare every 2 week to every 3 week dosing. Part C of the study will explore the safety, tolerability, and efficacy of the drug in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will explore the low and high doses of study drug identified in Parts A and B in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) will explore low, medium, and high doses of study drug in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will explore low and high doses of study drug in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. In Parts D and F and some of Part B participants will be randomized to one dose level. The primary hypotheses are the following: that pembrolizumab has acceptable safety and tolerability; and that pembrolizumab shows a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not), and a clinically meaningful RR in participants with NSCLC, especially a clinically meaningful RR in those participants with either cancer, whose tumors express PD-L1.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria (Part F is the only part currently enrolling participants)

  • In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC. In Part F, participants with Stage IV NSCLC without prior systemic therapy may be eligible.
  • Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy.
  • In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging.
  • In Part F of the study, NSCLC with PD-L1 gene expression.
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Adequate organ function.
  • Female participants of childbearing potential should have a negative urine or serum pregnancy test prior to receiving study medication
  • Female participants of childbearing potential must be willing to use adequate contraception from study start, through the course of the study, and for 120 days after the last dose of study medication
  • Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication through 120 days after the last dose of study medication

Exclusion Criteria (Part F is the only part currently enrolling participants)

  • Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose.
  • Participation in a study of an investigational agent or using an investigational device within 30 days of administration of pembrolizumab, with the exception of participants in the follow-up phase.
  • Other form(s) of antineoplastic therapy anticipated during the period of the study.
  • History of pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
  • Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids.
  • History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis.
  • History of a hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or another malignant primary solid tumor, unless no evidence of that disease for 5 years.
  • Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
  • Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents, except vitiligo or resolved childhood asthma/atopy.
  • Prior therapy with another anti-programmed cell death (PD)-1 agent or previously enrolled in any pembrolizumab trial.
  • Active infection requiring therapy.
  • Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid [HCV RNA] (qualitative) is detected).
  • Regular use of illicit drugs or a recent history (within the last year) of substance abuse (including alcohol).
  • Symptomatic ascites or pleural effusion.
  • Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Roxana Dronca, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Roxana Dronca, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Roxana Dronca, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20116098

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