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)
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.
Arms & interventions
- BiologicalPembrolizumab
IV infusion
Outcome measures
Primary
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 2 years
Secondary
ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)
Time frame: 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)
Time frame: Up to approximately 2 years
DOR per RECIST 1.1 by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)
Time frame: Up to approximately 2 years
DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort)
Time frame: Up to approximately 2 years
DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort)
Time frame: Up to approximately 2 years
DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
Time frame: Up to approximately 2 years
DOR per irRECIST by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)
Time frame: Up to approximately 2 years
Progression-free Survival (PFS) Using RECIST 1.1 Criteria by Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
Time frame: Up to approximately 2 years
PFS using RECIST 1.1 Criteria by Site Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
Time frame: Up to approximately 2 years
PFS using IWG 2007 Criteria (Chesson 2007) by BICR Assessment (rrcHL Cohort)
Time frame: Up to approximately 2 years
PFS using IWG 2007 Criteria (Chesson, 2007) by Site Assessment (rrcHL Cohort)
Time frame: Up to approximately 2 years
PFS Using irRECIST Criteria by Site Assessment
Time frame: Up to approximately 2 years
Disease Control Rate by RECIST 1.1 Using Site Assessment (Solid Tumors and Other Lymphoma, Each Disease Indication Evaluated Separately)
Time frame: Up to approximately 2 years
Disease Control Rate by RECIST 1.1 Using Site Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
Time frame: Up to approximately 2 years
Disease Control Rate by irRECIST Using Site Assessment (Solid Tumors and Other Lymphomas, Each Disease Indication Evaluated Separately)
Time frame: Up to approximately 2 years
Overall Survival
Time frame: Up to approximately 2 years
Objective irRECIST Response Rate by Site Assessment (Each Disease Indication Evaluated Separately)
Time frame: Up to approximately 2 years
Area Under the Concentration Curve (AUC) for Pembrolizumab
Time frame: 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
Eligibility criteria
Study locations (7)
Call for Information (Investigational Site 0019)
Aurora, Colorado, 80045
Call for Information (Investigational Site 0024)
Chicago, Illinois, 60637
Call for Information (Investigational Site 0026)
Boston, Massachusetts, 02445
Call for Information (Investigational Site 0031)
New York, New York, 10032
Call for Information (Investigational Site 0070)
Fargo, North Dakota, 58102
Call for Information (Investigational Site 0071)
Sioux Falls, South Dakota, 57117
Call for Information (Investigational Site 0054)
Dallas, Texas, 75235
References
- 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.(PubMed)