A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02332668
Recruitment Status : Recruiting
First Posted : January 7, 2015
Last Update Posted : July 12, 2018
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer:

  • advanced melanoma (6 months to <18 years of age),
  • advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age),
  • relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or
  • advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6 months to <18 years of age).

Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D.

The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer.

Condition or disease Intervention/treatment Phase
Melanoma Lymphoma Solid Tumor Classical Hodgkin Lymphoma Microsatellite-instability-high Solid Tumor Biological: Pembrolizumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Pembrolizumab (MK-3475) in Children With Advanced Melanoma or a PD-L1 Positive Advanced, Relapsed or Refractory Solid Tumor or Lymphoma (KEYNOTE-051)
Actual Study Start Date : March 18, 2015
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2022

Arm Intervention/treatment
Experimental: Melanoma
Participants aged 6 months to <18 years with melanoma receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), intravenously (IV) once every 3 weeks (Q3W).
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475

Experimental: Solid Tumors and Other Lymphomas
Participants aged 6 months to <18 years with solid tumors and other lymphomas receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W. Initial enrollment limited to programmed death-ligand 1 (PD-L1)-positive participants. PD-L1-negative participants may enroll if responses are observed.
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475

Experimental: rrcHL
Participants aged 3 years to <18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475

Experimental: MSI-H
Participants aged 6 months to <18 years with microsatellite-instability-high (MSI-H) solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475

Primary Outcome Measures :
  1. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per Site Assessment (Melanoma, Solid Tumor and Lymphoma Participants) [ Time Frame: Up to 2 years ]
  2. Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up to 21 days) ]
  3. Area Under the Concentration Curve (AUC) for Pembrolizumab [ Time Frame: Predose Cycles 1, 2, 4, 8 and every 4 cycles thereafter, and within 30 minutes post infusion at Cycles 1 and 8. Additional single pharmacokinetic samples obtained in Cycle 1 between 72 to 168 hours post-dose, and Cycle 1 at 336 hours post-dose. ]
  4. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 27 months ]
  5. Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to 2 years ]
  6. ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per Blinded Independent Central Radiology Assessment (rrcHL Participants) [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Participants) [ Time Frame: Up to 2 years ]

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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
  • Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
  • Any number of prior treatment regimens
  • Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
  • Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
  • Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
  • Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
  • Adequate organ function
  • Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
  • Female participants of childbearing potential must be willing to use 2 methods of contraception 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
  • Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication

Exclusion Criteria:

  • Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
  • Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Prior radiotherapy within 2 weeks of start of study treatment
  • Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Tumor(s) involving the brain stem
  • Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
  • Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
  • Human immunodeficiency virus (HIV)
  • Hepatitis B or C
  • Known history of active tuberculosis (TB; Bacillus tuberculosis)
  • Received a live vaccine within 30 days of planned start of study medication
  • Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of Graft Versus Host Disease [GVHD].)
  • History or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
  • Known psychiatric or substance abuse disorders that would interfere with the requirements of the study

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 identifier (NCT number): NCT02332668

Contact: Toll Free Number 1-888-577-8839

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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT02332668     History of Changes
Other Study ID Numbers: 3475-051
2014-002950-38 ( EudraCT Number )
First Posted: January 7, 2015    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:

Additional relevant MeSH terms:
Hodgkin Disease
Microsatellite Instability
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Genomic Instability
Pathologic Processes
Antineoplastic Agents