Pembrolizumab for Pediatric Cancer

Recruiting in Palo Alto (17 mi)

+24 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, CNS metastases, Autoimmune, others

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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, enrolment of participants with solid tumours and participants 6 months to under 12 years old with melanoma were closed. Enrolment of participants 12-18 years old with melanoma continues. Enrolment of participants who have tumours with specific traits (microsatellite-instability-high (MSI-H), and tumour-mutational burden-high ≥10 mutation/Mb (TMB-H)) also continues.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for pediatric cancer?

Pembrolizumab has been approved for use in both adults and children with certain types of solid tumors that have specific genetic features (mismatch repair-deficient or microsatellite instability-high), showing a significant response rate in clinical trials. This approval is based on its effectiveness across various tumor types, not just one specific kind, which suggests it could be beneficial for pediatric cancers with these genetic markers. ^{1 2 3 4 5}

What safety information is available for pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with some immune-related side effects, including a rare risk of developing type 1 diabetes in 0.2% of cases and pneumonitis (lung inflammation) in 1%-5% of patients. Other common side effects include fatigue, cough, nausea, and rash. ^{1 3 5 6 7}

What makes the drug pembrolizumab unique for pediatric cancer treatment?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 receptor on T cells, which helps the immune system attack cancer cells more effectively. Unlike traditional chemotherapy, it specifically targets the immune system to fight cancer, and it is being studied for its safety and effectiveness in children with advanced cancer, where standard treatments may not be available. ^{1 3 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for children aged 6 months to <18 years with advanced solid tumors or lymphoma, including melanoma and Hodgkin's lymphoma. They must have failed previous treatments or have no standard treatment options available. Participants need adequate organ function and a negative pregnancy test if applicable. Those with active brain metastases, current pneumonitis, recent live vaccines, HIV, hepatitis B/C, or severe allergies to pembrolizumab are excluded.

Inclusion Criteria

I am not able to have children or I am using birth control and will not have heterosexual intercourse.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

My neuroblastoma shows up on a special scan.

Exclusion Criteria

I am currently on medication for an infection.

I had an organ transplant or a bone marrow transplant from a donor more than 5 years ago without GVHD symptoms.

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 date of allocation/randomization

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab, an immunotherapy, to evaluate its effect on advanced melanoma, solid tumors, and lymphomas

Up to 27 months

IV administration every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Pembrolizumab (Checkpoint Inhibitor)

Trial Overview The study tests Pembrolizumab (MK-3475), an immunotherapy drug for pediatric cancer patients. It has two parts: the first part determines the safest dose for children while the second evaluates its effectiveness at that dose against various types of advanced cancers in kids.

Participant Groups

Group I: rrcHL Experimental Treatment 1 Intervention

Participants aged 3 years to \<18 years with rrcHL receive pembrolizumab, starting dose 2 mg/kg (maximum dose 200 mg), IV Q3W.

Group II: TMB-H Experimental Treatment 1 Intervention

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.

Group III: Solid Tumors and Other Lymphomas Experimental Treatment 1 Intervention

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.

Group IV: Melanoma Experimental Treatment 1 Intervention

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.

Group V: MSI-H Experimental Treatment 1 Intervention

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.

Group VI: Adjuvant Melanoma Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has received accelerated FDA approval for treating both adult and pediatric patients with solid tumors that are mismatch repair-deficient or microsatellite instability-high.

This approval marks a significant milestone as it is the first instance where the FDA has approved a cancer treatment based on a common biomarker rather than the specific type of tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Tissue-Agnostic Drug Approval Issued. [2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab was approved by the FDA for treating certain types of advanced cancers with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) characteristics, showing an overall response rate of 39.6% in a study of 149 patients across 15 tumor types.

This approval is significant as it marks the first time the FDA has authorized a cancer treatment based on a common biomarker rather than the specific type of cancer, highlighting the importance of genetic factors in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Marcus, L., Lemery, SJ., Keegan, P., et al.[2020]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

First Tissue-Agnostic Drug Approval Issued. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]