A Study of Pembrolizumab (MK-3475) in Pediatric Participants With Advanced Melanoma or Advanced, Relapsed, or Refractory PD-L1-Positive Solid Tumors or Lymphoma (MK-3475-051/KEYNOTE-051)

Status: Recruiting
DFCI Protocol ID: 16-235

This is a 2-part study of pembrolizumab (MK-3475) in pediatric participants who have either advanced melanoma or a programmed cell death ligand 1 (PD-L1)-positive advanced, relapsed or refractory solid tumor or lymphoma. 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

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Steven Dubois MD, Dana Farber Cancer Institute

Site-responsible Investigators:


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Between 6 months and less than 18 years of age 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

  -  Any number of prior treatment regimens

  -  Tissue 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

  -  Measurable disease based on RECIST 1.1

  -  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 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

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 first dose of study medication

  -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
     of immunosuppressive therapy within 7 days prior to the first dose of study

  -  Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not
     recovered adverse events due to mAbs administered more than 4 weeks earlier

  -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
     weeks prior to study Day 1 or not recovered from adverse events due to a previously
     administered agent

  -  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
     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

  -  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

  -  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

  -  Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (L1), or
     anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) agent, or any other
     antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

  -  Human immunodeficiency virus (HIV)

  -  Hepatitis B or C

  -  Received a live vaccine within 30 days of planned start of study medication

  -  Has undergone solid organ transplant at any time, or prior allogeneic hematopoetic
     stem cell transplantation within the last 5 years. (Participants who have had a
     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 trial

  -  Known psychiatric or substance abuse disorders that would interfere with the
     requirements of the trial

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