Clinical Trials /

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

NCT02332668

Description:

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. With Amendment 8, enrollment of participants with solid tumors and of participants aged 6 months to <12 years with melanoma were closed. Enrollment of participants aged ≥12 years to ≤18 years with melanoma continues. Enrollment of participants with MSI-H solid tumors also continues.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 3475-051
  • SECONDARY ID: 2014-002950-38
  • NCT ID: NCT02332668

Conditions

  • Melanoma
  • Lymphoma
  • Solid Tumor
  • Classical Hodgkin Lymphoma
  • Microsatellite-instability-high Solid Tumor

Interventions

DrugSynonymsArms
PembrolizumabMK-3475Melanoma

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
MelanomaExperimentalParticipants 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).
    Solid Tumors and Other LymphomasExperimentalParticipants 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.
      rrcHLExperimentalParticipants aged 3 years to <18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
        MSI-HExperimentalParticipants 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.

          Eligibility Criteria

                  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
                
          Maximum Eligible Age:17 Years
          Minimum Eligible Age:6 Months
          Eligible Gender:All
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure: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
          Safety Issue:
          Description:

          Secondary Outcome Measures

          Measure:ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Participants)
          Time Frame:Up to 2 years
          Safety Issue:
          Description:

          Details

          Phase:Phase 1/Phase 2
          Primary Purpose:Interventional
          Overall Status:Recruiting
          Lead Sponsor:Merck Sharp & Dohme Corp.

          Trial Keywords

          • PD1
          • PD-1
          • PDL1
          • PD-L1
          • cHL
          • MSI-H

          Last Updated

          January 11, 2018