Pembrolizumab for Pediatric Cancer

Recruiting at 33 trial locations

Overseen By Toll Free Number

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, CNS metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 27 months

370 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy that aids the immune system in fighting cancer, to determine its effectiveness in shrinking or eliminating various pediatric cancers. It targets advanced, relapsed, or refractory cases of melanoma (skin cancer), solid tumors, and lymphomas (blood cancers) in children. Participants aged 12 to 18 with melanoma, or tumors with specific traits like microsatellite-instability-high (MSI-H) or high tumor-mutational burden (TMB-H), can join. The trial aims to identify the optimal dose of pembrolizumab for these conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that pembrolizumab is generally well-tolerated in both adults and children, with similar side effects in both groups. Common side effects may occur, but serious reactions are rare. In some studies, serious side effects like severe anemia (a condition with fewer red blood cells than normal) occurred in about 17% of cases. Fatal reactions are very rare, occurring in about 1.3% of patients, due to unknown causes, severe infections, and immune-related lung disease.

While pembrolizumab is already approved for treating some types of cancer in adults, its safety and effectiveness in children remain under study. The similar safety profile in adults offers researchers hope for its use in children. Joining a clinical trial means participating in important research that could benefit many others in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab for pediatric cancer because it works differently from many current treatments. Unlike traditional chemotherapy, which attacks rapidly dividing cells, pembrolizumab is an immunotherapy that empowers the body's own immune system to fight cancer by blocking a protein called PD-1, which tumors use to hide from immune cells. This mechanism can potentially offer a more targeted approach with fewer side effects. Additionally, pembrolizumab's ability to target specific cancer markers like MSI-H and TMB-H makes it a promising option for personalized medicine, providing hope for better outcomes in young patients with difficult-to-treat tumors.

What evidence suggests that this trial's treatments could be effective for pediatric cancer?

Research has shown that pembrolizumab, a treatment that aids the immune system in fighting cancer, can be effective against various cancer types. In this trial, participants with classical Hodgkin lymphoma that has returned or not responded to other treatments (rrcHL) will receive pembrolizumab. Studies found that 69% responded to pembrolizumab, with some achieving complete remission, meaning no signs of cancer were found. For participants with certain solid tumors with specific genetic features called microsatellite instability-high (MSI-H), pembrolizumab has shown positive results, leading to its approval for treating both adults and children with these tumors. In this trial, participants with melanoma will also receive pembrolizumab, which has significantly improved survival rates, with one-third of patients still alive after ten years. Additionally, for tumors with a high number of genetic changes (high tumor-mutational burden, or TMB-H), pembrolizumab showed promise, leading to FDA approval for its use in children. Overall, these encouraging outcomes support pembrolizumab's ability to help the immune system fight cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

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.

How Is the Trial Designed?

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).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Published Research Related to This Trial

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 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]

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 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, 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 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]

In a study involving 154 pediatric patients with advanced cancer, pembrolizumab was found to be well tolerated, with no dose-limiting toxicities reported, establishing a recommended phase 2 dose of 2 mg/kg every 3 weeks.

While pembrolizumab showed promising antitumor activity in patients with relapsed or refractory Hodgkin lymphoma (60% objective response rate), it demonstrated low efficacy in most other pediatric tumor types, indicating that PD-L1 expression alone may not be a reliable biomarker for predicting treatment response.

NCBI (Pubmed)

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. Geoerger, B., Kang, HJ., Yalon-Oren, M., et al.[2020]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10941196/

Pembrolizumab versus placebo as adjuvant therapy in ... Adjuvant pembrolizumab was shown to significantly improve recurrence-free survival and distant metastasis-free survival compared with placebo in ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1802357

Adjuvant Pembrolizumab versus Placebo in Resected ... Pembrolizumab has been found to be associated with longer progression-free survival and overall survival in advanced melanoma than ipilimumab.

3. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02355

Pembrolizumab Versus Placebo as Adjuvant Therapy in ... Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03553836

NCT03553836 | Safety and Efficacy of Pembrolizumab ... This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk ...

6. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf ... and Grade 3 anemia (17%). The safety and effectiveness of KEYTRUDA in pediatric patients have not been established in the other approved indications [see ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7576004/

Pembrolizumab (and friends) in pediatric malignancies The safety profile of pembrolizumab in children was similar to those recorded in the adult population. Treatment-related adverse events (AEs) of any grade were ...

8. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Fatal adverse reactions occurred in 1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%).

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204519306710

Pembrolizumab in paediatric patients with advanced ... Pembrolizumab is approved for the treatment of advanced cancer in adults; however, no information is available on safety and efficacy in paediatric patients. We ...

10. keytruda.com keytruda.com/

KEYTRUDA® (pembrolizumab) - Official Site TREATS 18 TYPES OF CANCER, INCLUDING CERTAIN EARLY-STAGE AND ADVANCED CANCERS. ONE OF THOSE CANCERS IS EARLY-STAGE NON—SMALL CELL LUNG CANCER (NSCLC).