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

NCT02332668 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 3475-051MK-3475-0512022-501257-36-00U1111-1275-95162014-002950-38
• Study Type: interventional
• Target: 370
• Locations: 11 countries
• Sites: 17

Brief Summary

Researchers are looking for new ways to treat children with different types of melanoma (skin cancer), solid tumors, and lymphomas (blood cancers) that are any of these:

• Advanced, which means cancer spread in the body or cannot be removed with surgery
• Relapsed, which means cancer has come back after it had responded to previous treatment (responded means it stopped growing, gets smaller, or disappeared)
• Refractory, which means cancer did not respond to previous treatment Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Researchers want to learn if different doses of pembrolizumab can cause at least 1 of the types of cancer to get smaller or go away. With Amendment 8, enrollment of participants with solid tumors and participants 6 months to under 12 years old with melanoma were closed. With Amendment 13, enrollment was closed for participants with relapsed refractory classical Hodgkin lymphoma (rrCHL), microsatellite instabilty-high (MSI-H) solid tumors, tumor-mutational burden-high (TMB-H) solid tumors, and participants 12 years old to \<18 years old with advanced melanoma.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors and Other Lymphoma Version 1.1 (RECIST 1.1) per Site Assessment (Each Disease Indication Evaluated Separately)

  The ORR is assessed by RECIST 1.1 per site assessment. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 2 years

• ORR by RECIST 1.1 per Site Assessment for MSI-H or TMBH Solid Tumors (Each Cohort Evaluated Separately)

  The ORR is assessed by RECIST 1.1 per site assessment. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 2 years

• ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per Blinded Independent Central Review (BICR) Assessment for rrcHL Cohort

  The ORR is assessed by blinded independent central review utilizing the International Working Group \[IWG\] response assessment criteria per Cheson 2007 by BICR. The ORR is defined as the percentage of participants who have a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data are considered non-responders.

  Up to approximately 2 years

• Number of Participants with Dose-Limiting Toxicities (DLTs)

  Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose.

  Cycle 1 (Up to 21 days)

• Number of Participants Experiencing Adverse Events (AEs)

  An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to 27 months

• Number of Participants Discontinuing Study Drug Due to AEs

  An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to 2 years

Secondary Outcomes (18)

• ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)

  Up to 2 years

• DOR per RECIST 1.1 by Site Assessment (Advanced Melanoma, Solid Tumors and Other Lymphoma, Each Disease Indication Is Evaluated Separately)

  Up to approximately 2 years

• DOR per RECIST 1.1 by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)

  Up to approximately 2 years

• DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort)

  Up to approximately 2 years

• DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort)

  Up to approximately 2 years

Study Arms (6)

Melanoma

EXPERIMENTAL

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). Enrollment of participants aged 6 months to \<12 years with melanoma was closed with Amendment 8. Enrollment of participants aged ≥12 years to ≤18 years with melanoma closed with Amendment 13.

Biological: Pembrolizumab

Solid Tumors and Other Lymphomas

EXPERIMENTAL

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. Enrollment of participants with solid tumors and other lymphomas was closed with Amendment 8.

Biological: Pembrolizumab

Relapsed Refractory Classical Hodgkin Lymphoma (rrcHL)

EXPERIMENTAL

Participants aged 3 years to \<18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W. Enrollment of participants with rrcHL was closed with Amendment 13.

Biological: Pembrolizumab

Microsatellite Instability-High (MSI-H)

EXPERIMENTAL

Participants aged 6 months to \<18 years with MSI-H solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W. Enrollment of participants with MSI-H solid tumors was closed with Amendment 13.

Biological: Pembrolizumab

Tumor Mutational Burden-High (TMB-H)

EXPERIMENTAL

Participants aged 6 months to \<18 years with TMB-H ≥10 mutation/Mb solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W. Enrollment of participants with TMB-H solid tumors was closed with Amendment 13.

Biological: Pembrolizumab

Adjuvant Melanoma

EXPERIMENTAL

Participants aged 12 years to \<18 years with resected high-risk Stage IIB, IIC, III, or IV melanoma receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), intravenously (IV) once every 3 weeks (Q3W).

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475

Adjuvant Melanoma; Melanoma; Microsatellite Instability-High (MSI-H); Relapsed Refractory Classical Hodgkin Lymphoma (rrcHL); Solid Tumors and Other Lymphomas; Tumor Mutational Burden-High (TMB-H)

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Between 6 months and \<18 years of age on day of signing informed consent is documented.
• 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 before the first dose of study medication
• Female participant is not a woman of childbearing potential (WOCBP) or is a WOCBP who is abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of study intervention
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Demonstrate adequate organ function.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (17)

Call for Information (Investigational Site 0019)

Aurora, Colorado, 80045, United States

RECRUITING

Call for Information (Investigational Site 0026)

Boston, Massachusetts, 02445, United States

RECRUITING

Call for Information (Investigational Site 0031)

New York, New York, 10032, United States

RECRUITING

Call for Information (Investigational Site 0070)

Fargo, North Dakota, 58102, United States

RECRUITING

Call for Information (Investigational Site 0032)

Cincinnati, Ohio, 45229, United States

RECRUITING

Call for Information (Investigational Site 0071)

Sioux Falls, South Dakota, 57117, United States

RECRUITING

Call for Information (Investigational Site 0054)

Dallas, Texas, 75235, United States

RECRUITING

MSD Brasil

São Paulo, Brazil

RECRUITING

MSD France

Paris, France

RECRUITING

MSD Sharp & Dohme GmbH

München, Germany

RECRUITING

Merck Sharp & Dohme Co. Ltd.

Hod HaSharon, Israel

RECRUITING

MSD Italia S.r.l.

Rome, Italy

RECRUITING

Merck Sharp & Dohme BV

Haarlem, Netherlands

RECRUITING

Merck Sharp & Dohme Lda.

Paço de Arcos, Portugal

RECRUITING

MSD Korea LTD

Seoul, 4130, South Korea

RECRUITING

MSD Sweden

Stockholm, Sweden

RECRUITING

Merck Sharp & Dohme Ltd.

London, United Kingdom

RECRUITING

Related Publications (1)

• Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo A, Laetsch TW, Petrilli AS, Ebinger M, Toporski J, Glade-Bender J, Nicholls W, Fox E, DuBois SG, Macy ME, Cohn SL, Pathiraja K, Diede SJ, Ebbinghaus S, Pinto N. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Jan;21(1):121-133. doi: 10.1016/S1470-2045(19)30671-0. Epub 2019 Dec 4.

  PMID: 31812554 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Melanoma; Lymphoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 7, 2015
• Study Start: March 19, 2015
• Primary Completion (Estimated): February 2, 2028
• Study Completion (Estimated): February 2, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

PT (1); IL (1); DE (1); BR (1); NL (1); US (7); SE (1); IT (1); KR (1); FR (1); GB (1)