A Study of Pembrolizumab (MK-3475) in Pediatric Participa... | NCT02332668

NCT02332668

ID	Type	Description
MK-3475-051	Other Identifier	MSD Protocol Number
2022-501257-36-00	Registry Identifier	EU CT
U1111-1275-9516	Registry Identifier	UTN
2014-002950-38	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	IV infusion	Adjuvant Melanoma Melanoma Microsatellite Instability-High (MSI-H) Relapsed Refractory Classical Hodgkin Lymphoma (rrcHL)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)

Secondary Outcomes

Measure	Description	Time Frame
ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)	The ORR is assessed by blinded independent central review utilizing the International Working Group [IWG] response assessment criteria per Cheson 2007 by site assessment. The ORR is defined as the percentage of participants who had 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

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

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases