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

Summary:

This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer: - advanced melanoma (6 months to <18 years of age), - advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumour or other lymphoma (6 months to <18 years of age), - relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or - advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumours (6 months to <18 years of age), or - advanced relapsed or refractory tumour-mutational burden-high ≥10 mutation/Mb (TMB-H) solid tumours (6 months to <18 years of age) Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D. The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumour or other lymphoma; advanced, relapsed or refractory MSI-H solid tumour; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer. The 10% assessment does not apply to the MSI-H and TMB-H cohorts. With Amendment 8, enrollment of participants with solid tumours and of participants aged 6 months to <12 years with melanoma were closed. Enrollment of participants aged ≥12 years to ≤18 years with melanoma continues. Enrollment of participants with MSI-H and TMB-H solid tumours also continues.

Trial Description

Primary Outcome:

  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumours and Other Lymphoma Version 1.1 (RECIST 1.1) per Site Assessment (Each Disease Indication Evaluated Separately)
  • ORR per RECIST 1.1 by Blinded Independent Central Review (BICR) Assessment for MSI-H or TMBH Solid Tumours (Each Cohort Evaluated Separately)
  • ORR by International Working Group (IWG) Response Criteria (Cheson, 2007) per BICR Assessment for rrcHL Cohort
  • Number of Participants with Dose-Limiting Toxicities (DLTs)
  • Number of Participants Experiencing Adverse Events (AEs)
  • Number of Participants Discontinuing Study Drug Due to AEs
Secondary Outcome:
  • ORR per RECIST 1.1 by Site Assessment for MSI-H or TMBH Solid Tumours (Each Cohort Is Evaluated Separately)
  • ORR by IWG Response Criteria (Cheson, 2007) per Site Assessment (rrcHL Cohort)
  • DOR per RECIST 1.1 by BICR Assessment
  • DOR per RECIST 1.1 by Site Assessment (Solid Tumours and Other Lymphoma, Each Disease Indication Is Evaluated Separately)
  • DOR per RECIST 1.1 by BICR Assessment (MSI-H and TMBH, Each Cohort Evaluated Separately)
  • DOR per RECIST 1.1 by Site Assessment (MSI-H and TMBH, Each Cohort Is Evaluated Separately)
  • DOR per IWG 2007 (Cheson, 2007) Response by BICR Assessment (rrcHL Cohort)
  • DOR per IWG 2007 (Cheson, 2007) Response by Site Assessment (rrcHL Cohort)
  • DOR per Immune-related Response Evaluation Criteria in Solid Tumours (irRECIST) by Site Assessment (Solid Tumours and Other Lymphoma, Each Disease Indication Evaluated Separately)
  • DOR per Immune-related Response Evaluation Criteria in Solid Tumours (irRECIST) by Site Assessment (MSI-H and TMB-H, Each Cohort Is Evaluated Separately)
  • Progression-free Survival (PFS) Using RECIST 1.1 Criteria by Site Assessment (Solid Tumours and Other Lymphoma, Each Disease Indication Evaluated Separately)
  • PFS using RECIST 1.1 Criteria by BICR Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
  • PFS using RECIST 1.1 Criteria by Site Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
  • PFS using IWG 2007 Criteria (Chesson 2007) by BICR Assessment (rrcHL Cohort)
  • PFS using IWG 2007 Criteria (Chesson, 2007) by Site Assessment (rrcHL Cohort)
  • PFS Using irRECIST Criteria by Site Assessment
  • Disease Control Rate by RECIST 1.1 Using Site Assessment (Solid Tumours and Other Lymphoma, Each Disease Indication Evaluated Separately)
  • Disease Control Rate by RECIST 1.1 Using BICR Assessment (MSI-H and TMB-H, Each Cohort Evaluated Separately)
  • Disease Control Rate by RECIST 1.1 Using Site Assessment (MSIH and TMB-H, Each Cohort Evaluated Separately)
  • Disease Control Rate by irRECIST Using Site Assessment (Solid Tumours and Other Lymphomas, Each Disease Indication Evaluated Separately)
  • Overall Survival
  • Objective irRECIST Response Rate by Site Assessment (Each Disease Indication Evaluated Separately)
  • Area Under the Concentration Curve (AUC) for Pembrolizumab

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society