ADVL1621: 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)

Why are we doing this research?

PURPOSE:

This is a 2-part study of pembrolizumab (MK-3475) in pediatric participants who have either advanced melanoma or a programmed cell death ligand 1 (PD-L1)-positive advanced, relapsed or refractory solid tumor or lymphoma. 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.


DETAILED DESCRIPTION:

  • PRIMARY OBJECTIVES:
  • Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per Site Assessment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up to 21 days) ] [ Designated as safety issue: Yes ]
  • 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 PK samples in Cycle 1 between 72 to 168 hours post-dose, and Cycle 1 at 336 hours post-dose. ] [ Designated as safety issue: No ]
  • Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Study Type: Interventional
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment

Masking: Open Label
Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 6 Months to 17 Years

ELIGIBILITY CRITERIA

Inclusion Criteria:

  • Between 6 months and less than 18 years of age on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be >= 6 years of age)
  • 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 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
  • Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
  • 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 first dose of study medication
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered adverse events due to mAbs administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • 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 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
  • 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
  • Human immunodeficiency virus (HIV)
  • Hepatitis B or C
  • Received a live vaccine within 30 days of planned start of study medication
  • Has undergone solid organ transplant at any time, or prior allogeneic hematopoetic stem cell transplantation within the last 5 years. (Participants who have had a 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 trial
  • Known psychiatric or substance abuse disorders that would interfere with the requirements of the trial

Conditions

  • Lymphoma Hodgkin Relapse
  • Lymphoma Non Hodgkin Relapse
  • Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Sarcoma Ewing Relapse
  • Sarcoma Osteosarcoma Relapse
  • Sarcoma Rhabdomyosarcoma Relapse
  • Neuroblastoma Relapse - Refractory
  • Liver Relapse - Refractory
  • Kidney Relapse - Refractory
  • Solid Tumors - All Other
  • Solid Tumor Retinoblastoma Relapse - Refractory
  • Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Solid Tumor Melanoma Relapse - Refractory
  • Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Adult - Lymphoma Non Hodgkin Relapse
  • Adult - Lymphoma Hodgkin Relapse
  • Adult - Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Adult - Sarcoma Ewing Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Rhabdomyosarcoma Relapse
  • Adult - Neuroblastoma Relapse - Refractory
  • Adult - Liver Relapse - Refractory
  • Adult - Kidney Relapse - Refractory
  • Adult - Solid Tumor Retinoblastoma Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Solid Tumor Melanoma Relapse - Refractory
  • Adult - Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Adult - Solid Tumors - All Other

Contact

For more information contact:

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati OH 45229-3039

Phone: 513-636-2799
cancer@cchmc.org