Clinical trial NCT02332668: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Melanoma
Lymphoma
Solid Tumor
Classical Hodgkin Lymphoma
Microsatellite-instability-high Solid Tumor
Keywords: PD1
PD-1
PDL1
PD-L1
cHL
MSI-H
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-01-07
Enrollment: 370
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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, enrolment of participants with solid tumours and participants 6 months to under 12 years old with melanoma were closed. Enrolment of participants 12-18 years old with melanoma continues. Enrolment of participants who have tumours with specific traits (microsatellite-instability-high (MSI-H), and tumour-mutational burden-high ≥10 mutation/Mb (TMB-H)) also continues.


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

Primary outcomes:
measure: 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)
timeFrame: Up to 2 years
measure: ORR by RECIST 1.1 per Site Assessment for MSI-H or TMBH Solid Tumors (Each Cohort Evaluated Separately)
timeFrame: Up to 2 years
measure: ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per BICR Assessment for rrcHL Cohort
timeFrame: Up to approximately 2 years
measure: Number of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Up to 21 days)
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 27 months
measure: Number of Participants Discontinuing Study Drug Due to AEs
timeFrame: Up to 2 years
Secondary outcomes:
measure: ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)
timeFrame: Up to 2 years
measure: DOR per RECIST 1.1 by Site Assessment (Advanced Melanoma, Solid Tumors and Other Lymphoma, Each Disease Indication Is Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: DOR per RECIST 1.1 by Site Assessment (MSI-H and TMBH, Each Cohort Is Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort)
timeFrame: Up to approximately 2 years
measure: DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort)
timeFrame: Up to approximately 2 years
measure: DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: Progression-free Survival (PFS) Using RECIST 1.1 Criteria by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: PFS using RECIST 1.1 Criteria by Site Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: PFS using IWG 2007 Criteria (Chesson 2007) by BICR Assessment (rrcHL Cohort)
timeFrame: Up to approximately 2 years
measure: PFS using IWG 2007 Criteria (Chesson, 2007) by Site Assessment (rrcHL Cohort)
timeFrame: Up to approximately 2 years
measure: PFS Using irRECIST Criteria by Site Assessment
timeFrame: Up to approximately 2 years
measure: Disease Control Rate by RECIST 1.1 Using Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate by RECIST 1.1 Using Site Assessment (MSIH and TMB-H, Each Cohort Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate by irRECIST Using Site Assessment (Solid Tumors and Other Lymphomas, Each Disease Indication Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: Overall Survival
timeFrame: Up to approximately 2 years
measure: Objective irRECIST Response Rate by Site Assessment (Each Disease Indication Evaluated Separately)
timeFrame: Up to approximately 2 years
measure: Area Under the Concentration Curve (AUC) for Pembrolizumab
timeFrame: Predose Cycles 1, 2, 4, 8 and every 4 cycles thereafter, and within 30 minutes post infusion at Cycles 1 and 8. Additional single pharmacokinetic samples obtained in Cycle 1 between 72 to 168 hours post-dose, and Cycle 1 at 336 hours post-dose
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Call for Information (Investigational Site 0019)
state: Colorado
city: Boston
country: United States
facility: Call for Information (Investigational Site 0026)
state: Massachusetts
city: New York
country: United States
facility: Call for Information (Investigational Site 0031)
state: New York
city: Fargo
country: United States
facility: Call for Information (Investigational Site 0070)
state: North Dakota
city: Sioux Falls
country: United States
facility: Call for Information (Investigational Site 0071)
state: South Dakota
city: Dallas
country: United States
facility: Call for Information (Investigational Site 0054)
state: Texas
city: Sao Paulo
country: Brazil
facility: MSD Brasil
city: Paris
country: France
facility: MSD France
city: München
country: Germany
facility: MSD Sharp & Dohme GmbH
city: Hod Hasharon
country: Israel
facility: Merck Sharp & Dohme Co. Ltd.
city: Rome
country: Italy
facility: MSD Italia S.r.l.
city: Seoul
country: Korea, Republic of
facility: MSD Korea LTD
city: Haarlem
country: Netherlands
facility: Merck Sharp & Dohme BV
city: Paco D'arcos
country: Portugal
facility: Merck Sharp & Dohme Lda.
city: Stockholm
country: Sweden
facility: MSD Sweden
city: London
country: United Kingdom
facility: Merck Sharp & Dohme Ltd.
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.