MEKPEM: A Phase I/II trial of MK-3475 (pembrolizumab) in children’s solid tumors and lymphomas

Brief Summary

This study will assess the activity of pembrolizumab in pediatric tumors, especially in patients with advanced, relapsed, or refractory MSIH or TMB-H (non-MSI-H) solid tumors, and those with resected high-risk Stage IIB, IIC, III, or IV melanoma eligible for adjuvant treatment.

Results from the Part I dose finding and confirmation approach in this study will be used for an initial benefit-risk assessment, which in turn would support the generation of additional data in Part II of this study.

Part II focuses on the solid tumors most likely to show improvement, including advanced melanoma, advanced relapsed or refractory solid tumors or other lymphoma that are shown to be PD-L1 positive and advanced, relapsed or refractory MSI-H solid tumors, for which no effective treatment is currently known.

Primary Objectives

• Test the safety and anti-tumor activity of pembrolizumab (formerly called MK-3475)
• To learn more about the side effects of pembrolizumab
• Look for the highest dose of pembrolizumab that can be given safely without serious side effects
• Find out how pembrolizumab is absorbed and broken down

Inclusion criteria (among others)

• Between 6 months and 18 years old (at pre-screening) with diagnosis of MSI-H solid tumor OR
• Between 3 and 18 years old (at pre-screening) with relapsed or refractory classical Hodgkin lymphoma OR
• Between 12 and 18 years old with diagnosis of melanoma  OR
• Between 12 and 18 years old with surgically and histologically/pathologically confirmed new diagnosis of Stage IIB, IIC, III, or IV melanoma, had no other treatment beyond surgical resection (no radiation treatment), no metastatic disease, and recovered completely from toxicity and surgery complications. 
• Participants of child bearing potential: negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Appropriate liver and kidney function as determined by protocol specific lab value criteria (see protocol for lab specific lab values)

Exclusion criteria (among others)

• 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 four weeks of the first dose of study treatment
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any form of immunosuppressive therapy within seven days prior to the first dose of trial treatment
  Note: The use of physiologic doses of corticosteroids (up to 5mg/m²_/day prednisone equivalent) may be approved after consultation with the Sponsor.
• Known additional malignancy that is progressing or requires active treatment.
  Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer).
• Active autoimmune disease that has required systemic treatment in past two (2) years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
  Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

About this study

This study will enroll participants who have melanoma or other solid tumors or lymphoma that is growing or has come back after receiving standard therapy. People with these conditions are usually treated with surgeries and/or chemotherapy using drugs approved by the U.S. Food and Drug Administration (FDA) because there is no standard therapy for this type of cancer. The drug in this study is called pembrolizumab.

Before enrolling, prospective participants will be screened. This process will include certain exams, tests, or procedures to make sure this study is a good option for them.

Purpose of this clinical trial

The main goal of the study is to see how safe and effective pembrolizumab is in treating children with these conditions. Researchers also want to learn the good and bad side effects of this medicine.

Eligibility overview

• Between 6 months and 18 years old with diagnosis of MSI-H solid tumor OR
• Between 3 and 18 years old with relapsed or refractory classical Hodgkin lymphoma OR
• Between 12 and 18 years old with diagnosis of melanoma OR
•  Between 12 and 18 years old with a diagnosis of Stage IIB, IIC, III, or IV melanoma, who had prior surgery to remove the tumor, but no other treatment (including radiation), no metastatic disease, and who have completely recovered.
• Negative pregnancy test 72 hours prior to medication administration in participants of child-bearing potential
• Appropriate liver and kidney functions