UCSF BTC Clinical Trials

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

Summary

The purpose of this Phase I/II clinical trial is to evaluate the dosage, safety and efficacy of pembrolizumab in treating pediatric participants with any of the following types of cancer:

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

Pembrolizumab is an antibody-based immunotherapy, administered intravenously, that targets the immune system and activates it to stop cancer growth and/or kill cancer cells. More specifically, pembrolizumab works by binding and inhibiting PD-1, a protein that normally protects the body from attacking itself. Normally, PD-1 works by detecting a molecular signal (called PDL-1) made by various cells across the body. Some cancer cells take advantage of this protection mechanism making the protective signal themselves. Blocking PD-1 with pembrolizumab allows the immune system to activate its T-cells and recognize these tumors as cells to be attacked.

In this phase I study, all eligible participants will receive the following treatment:

  • Experimental: Pembrolizumab

 

Inclusion Criteria
  1. 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)
  2. 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
  3. Any number of prior treatment regimens
  4. 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
  5. Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
  6. 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)
  7. Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
  8. 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
  9. Adequate organ function
  10. 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
  11. 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
  12. 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

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. 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 
  2. 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
  3. 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
  4. Prior radiotherapy within 2 weeks of start of study treatment
  5. 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
  6. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  7. Tumor(s) involving the brain stem
  8. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  9. 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
  10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  11. Active infection requiring systemic therapy
  12. 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
  13. 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)
  14. Human immunodeficiency virus (HIV)
  15. Hepatitis B or C 
  16. Known history of active tuberculosis (TB; Bacillus tuberculosis)
  17. Received a live vaccine within 30 days of planned start of study medication
  18. 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].)
  19. 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
  20. Known psychiatric or substance abuse disorders that would interfere with the requirements of the study

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

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