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1. 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) (Time Frame - Up to 2 years): 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.
2. ORR by RECIST 1.1 per Site Assessment for MSI-H or TMBH Solid Tumors (Each Cohort Evaluated Separately) (Time Frame - Up to 2 years): 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.
3. ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per BICR Assessment for rrcHL Cohort (Time Frame - Up to approximately 2 years): 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.
4. Number of Participants with Dose-Limiting Toxicities (DLTs) (Time Frame - Cycle 1 (Up to 21 days)): 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.
5. Number of Participants Experiencing Adverse Events (AEs) (Time Frame - Up to 27 months): 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.
6. Number of Participants Discontinuing Study Drug Due to AEs (Time Frame - Up to 2 years): 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.
Secondary outcome:
1. ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort) (Time Frame - Up to 2 years): 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.
2. 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): The duration of overall response is assessed by RECIST 1.1 by site evaluation. The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
3. DOR per RECIST 1.1 by Site Assessment (MSI-H and TMBH, Each Cohort Is Evaluated Separately) (Time Frame - Up to approximately 2 years): The duration of overall response is assessed by RECIST 1.1 by site evaluation. The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
4. DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort) (Time Frame - Up to approximately 2 years): The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
5. DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort) (Time Frame - Up to approximately 2 years): The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
6. 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): The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
7. DOR per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately) (Time Frame - Up to approximately 2 years): The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
8. 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): Progression free survival is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS is assessed by using RECIST 1.1 criteria by site assessment. Median PFS will be calculated from the product-limit (Kaplan-Meier) method for censored data.
9. 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): Progression free survival is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS is assessed by using RECIST 1.1 criteria by site assessment. Median PFS will be calculated from the product-limit (Kaplan-Meier) method for censored data.
10. PFS using IWG 2007 Criteria (Chesson 2007) by BICR Assessment (rrcHL Cohort) (Time Frame - Up to approximately 2 years): Progression free survival is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS is assessed by using IWG 2007 criteria (Chesson, 2007) by BICR assessment (rrcHL Cohort). Median PFS will be calculated from the product-limit (Kaplan-Meier) method for censored data.
11. PFS using IWG 2007 Criteria (Chesson, 2007) by Site Assessment (rrcHL Cohort) (Time Frame - Up to approximately 2 years): Progression free survival is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS is assessed by using IWG 2007 criteria (Chesson, 2007) by site assessment. Median PFS will be calculated from the product-limit (Kaplan-Meier) method for censored data.
12. PFS Using irRECIST Criteria by Site Assessment (Time Frame - Up to approximately 2 years): Progression free survival is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS is assessed by using irRECIST criteria by site assessment. Median PFS will be calculated from the product-limit (Kaplan-Meier) method for censored data.
13. 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 is defined as the percentage of participants with a response of CR, PR, or SD. 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. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease is least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
14. Disease Control Rate by RECIST 1.1 Using Site Assessment (MSIH and TMB-H, Each Cohort Evaluated Separately) (Time Frame - Up to approximately 2 years): Disease Control Rate is defined as the percentage of participants with a response of CR, PR, or SD. 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. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease is least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
15. 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): Disease Control Rate is defined as the percentage of participants with a response of CR, PR, or SD. 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. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease is least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
16. Overall Survival (Time Frame - Up to approximately 2 years): Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. Median overall survival will be calculated from the product-limit (Kaplan-Meier) method for censored data.
17. Objective irRECIST Response Rate by Site Assessment (Each Disease Indication Evaluated Separately) (Time Frame - Up to approximately 2 years): The ORR is assessed by irRECIST per site assessment.
18. 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): The AUC of pembrolizumab when administered as monotherapy will be determined.
Experimental: Melanoma 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 continues.
Experimental: Solid Tumors and Other Lymphomas 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.
Experimental: rrcHL Participants aged 3 years to <18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
Experimental: MSI-H Participants 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.
Experimental: TMB-H Participants aged 6 months to <18 years with tumor-mutational burden-high ≥10 mutation/Mb (TMB-H) solid tumors receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.
Experimental: Adjuvant Melanoma 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).
