Immunotherapy for Pediatric Liver Cancer

Recruiting at 4 trial locations

Overseen By DFCI Clinical Trials Hotline

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Allison O'Neill

Must not be taking: Checkpoint inhibitors, Antibody therapies, Steroids, Immunosuppressives

Disqualifiers: Autoimmune disease, HIV/AIDS, Organ transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 63 days

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy drug, to determine its effectiveness in treating certain types of liver cancer in children, specifically hepatocellular carcinoma and hepatocellular neoplasm not otherwise specified (HCN NOS). The goal is to assess the drug's ability to shrink tumors or halt their growth. This study suits patients under 30 with liver cancer that has recurred or is unresponsive to standard treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study drug. You must not have received standard or targeted treatments within 14 days, radiotherapy within 7 days, or antibody-based therapies within 3 half-lives of the last dose. Chronic steroids and anti-inflammatory or immunosuppressive medications are also not allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that pembrolizumab has been tested in various situations, including in children with liver cancer. One study used it with chemotherapy for children and young adults. The safety results showed it was generally well-tolerated, though some patients experienced side effects like tiredness and fever, common with treatments that boost the immune system.

Another study focused on adults with liver conditions. Most adults handled the treatment well, though some experienced mild to moderate side effects similar to those in younger patients.

While pembrolizumab is being tested in this trial, the FDA has already approved it for other uses. This approval indicates that, although side effects may occur, the drug's safety in humans is understood. Always consult a doctor about the potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pediatric liver cancer?

Pembrolizumab is unique because it enhances the body's immune response to target and destroy cancer cells. Unlike traditional chemotherapy, which directly attacks cancer cells but can also harm healthy cells, pembrolizumab works by blocking the PD-1 pathway. This allows the immune system to better recognize and fight cancer cells. Researchers are excited because this immunotherapy approach can potentially offer a more precise treatment with fewer side effects, and it represents a promising advancement for pediatric liver cancer, where treatment options are limited.

What evidence suggests that pembrolizumab might be an effective treatment for pediatric liver cancer?

Studies have shown that pembrolizumab, also known as KEYTRUDA, can help treat certain types of liver cancer. Research indicates that patients treated with pembrolizumab lived for about 14 to 15 months on average after starting treatment, suggesting it can extend life compared to some other treatments. Early findings suggest it might also benefit children, but more studies are needed. In this trial, participants will receive pembrolizumab, which boosts the body's immune system to fight cancer cells more effectively. ^{1 4 5 6 7}

Who Is on the Research Team?

Allison O'Neill, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and young adults under 30 with pediatric hepatocellular carcinoma or HCN NOS that's come back or didn't respond to treatment. They must have normal organ function, no recent radiation therapy, and not be on steroids or immunosuppressants. Participants need a negative pregnancy test if applicable and agree to use contraception.

Inclusion Criteria

- Lipase ≤ 1.5 x ULN

I am older than 16 years.

- Amylase ≤ 1.5 x ULN

Exclusion Criteria

Participants who are receiving any other investigational agents are not eligible.

Patients with prior solid organ transplantation are not eligible.

I am not taking any anti-inflammatory or immunosuppressive medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 3 weeks at a dose of 2mg/kg/dose (max: 200mg) with 21 consecutive days defined as a treatment cycle

63 days

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests Pembrolizumab (KEYTRUDA), an immunotherapy drug, as a potential treatment for liver cancer in the pediatric population. It aims to see how effective it is in treating relapsed/refractory cases of hepatocellular carcinoma in this age group.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab will be administered every 3 weeks at a dose of 2mg/kg/dose (max: 200mg) with 21 consecutive days defined as a treatment cycle.

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?

Allison O'Neill

Lead Sponsor

Trials

1

Recruited

20+

Allison O'Neill, MD

Lead Sponsor

Trials

1

Recruited

20+

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]

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]

In a phase III study involving 413 patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib, pembrolizumab showed a median overall survival of 13.9 months compared to 10.6 months for placebo, indicating its potential effectiveness as a treatment option.

While pembrolizumab demonstrated improved overall survival and progression-free survival compared to placebo, the study noted a higher incidence of grade 3 or higher adverse events, suggesting a need to weigh the benefits against the risks when considering this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. Finn, RS., Ryoo, BY., Merle, P., et al.[2020]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., 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]

In a phase 2 trial involving 104 patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib, pembrolizumab demonstrated an objective response rate of 17%, indicating its potential efficacy as a treatment option for this patient population.

While 73% of patients experienced treatment-related adverse events, most were manageable, with serious events occurring in 15% of patients, suggesting that pembrolizumab is generally tolerable for patients with advanced liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Zhu, AX., Finn, RS., Edeline, J., et al.[2022]

In a phase III trial involving 453 patients with advanced hepatocellular carcinoma (HCC), pembrolizumab significantly improved overall survival (14.6 months vs. 13.0 months for placebo) and progression-free survival (2.6 months vs. 2.3 months for placebo).

The objective response rate (ORR) was notably higher in the pembrolizumab group (12.7%) compared to the placebo group (1.3%), although treatment-related adverse events were more common in the pembrolizumab group (66.9% vs. 49.7% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. Qin, S., Chen, Z., Fang, W., 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]

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]

In a study of 29 patients with advanced hepatocellular carcinoma (HCC) treated with pembrolizumab, the overall response rate was 32%, with one complete response and eight partial responses, indicating that pembrolizumab can be an effective treatment option for this patient group.

The treatment was generally well-tolerated, with reversible grade 3/4 adverse events, and high baseline levels of TGF-β in plasma were identified as a potential predictive biomarker for poor treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma. Feun, LG., Li, YY., Wu, C., et al.[2020]

In a study of 491 oncology patients treated with pembrolizumab, 14.3% developed liver injury, with a median onset of 62 days, and those with liver injury had significantly poorer outcomes, including lower rates of tumor remission and higher mortality.

Only 28.6% of liver injury cases were confirmed as drug-induced hepatotoxicity, indicating that careful evaluation is necessary before administering corticosteroids, as these patients had better outcomes compared to those with unconfirmed liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Tsung, I., Dolan, R., Lao, CD., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6547263/

Pembrolizumab for the Treatment of Hepatocellular Carcinoma Safety data were also collected (Fig. 1). Efficacy Outcome. At the time of data cutoff on February 13, 2018, 17 (16%) subjects were still under treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04134559

Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma This research study is studying an immunotherapy drug (pembrolizumab or KEYTRUDA) as a possible treatment for pediatric hepatocellular carcinoma or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11145164/

Safety and Preliminary Efficacy of Pembrolizumab Following ... Fifteen patients were included in the safety and efficacy population: 73% had nonviral cirrhosis; median age was 72 years. Child-Pugh class was A in 14 patients ...

4. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-os-versus-placebo-in-certain-patients-with-advanced-hepatocellular-carcinoma-hcc-previously-treated-with-sora/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... For patients treated with KEYTRUDA plus BSC, median OS was 14.6 months (95% CI, 12.6-18.0) compared to 13.0 months (95% CI, 10.5-15.1) for ...

5. ascopubs.org ascopubs.org/doi/10.1200/GO-25-00128

Effectiveness and Safety of Immunotherapy for ... The median treatment duration was 4.9 months, and the median overall survival (OS) was 14.7 months (95% CI, 11.6 to 24.5), with 12- and 24-month ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03407144

NCT03407144 | Safety and Efficacy of Pembrolizumab (MK ... This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394043/

Safety and clinical efficacy of immune checkpoint inhibitors ... We collected data on two pediatric HCC cases diagnosed at the First Affiliated Hospital of Gannan Medical University between January 2020 and ...