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)

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 other 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.

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 appropriate
• 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 lymphoma
• 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 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 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 medication
• 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 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 (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 hematopoietic 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

Lead Organization
Merck and Company Inc