Pembrolizumab for Mesothelioma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active CNS metastases, Autoimmune disease, 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: 9

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a monoclonal antibody, to evaluate its effectiveness for individuals with malignant mesothelioma, a rare cancer affecting the lung or abdominal lining. Pembrolizumab boosts the immune system by blocking a protein that typically slows immune responses. The trial suits those whose mesothelioma has worsened after specific chemotherapy treatments and who have not undergone more than two prior lines of chemotherapy. Participants must be willing to provide a tumor sample for analysis and have a measurable form of the disease according to specific criteria. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

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

Research has shown that pembrolizumab is generally well-tolerated by patients. Studies have demonstrated its promise in treating malignant pleural mesothelioma, a cancer affecting the lung lining. This treatment blocks a protein that helps cancer cells evade the immune system, enabling the body to fight the cancer more effectively.

Most patients tolerate pembrolizumab well, but like any medication, it can cause side effects. These side effects are usually manageable, so it's important to inform the medical team about any concerns. The FDA has also approved pembrolizumab for other uses, which increases confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab for treating mesothelioma because it leverages the power of the immune system in a novel way. Unlike traditional chemotherapy, which directly targets and kills cancer cells, pembrolizumab is an immunotherapy that blocks a protein called PD-1. This action helps the immune system recognize and attack cancer cells more effectively. This innovative approach could offer a new lifeline for mesothelioma patients, potentially leading to longer-lasting responses and fewer side effects compared to chemotherapy.

What evidence suggests that pembrolizumab might be an effective treatment for mesothelioma?

Research shows that pembrolizumab, the treatment under study in this trial, might help treat malignant mesothelioma, a cancer affecting the lining of the lungs or abdomen. Studies found that 21% of patients experienced a partial response, meaning their cancer got smaller, and 53% had stable disease, meaning their cancer stopped growing. Pembrolizumab blocks a protein called PD-1, which helps the immune system fight cancer cells. Additionally, when combined with chemotherapy in other studies, pembrolizumab has helped patients live longer with related conditions, like malignant pleural mesothelioma. These findings suggest pembrolizumab could be a promising option for patients with this challenging type of cancer. ^{2 4 5 6 7}

Who Is on the Research Team?

Hedy Kindler, M.D.

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for patients with malignant mesothelioma who have seen their disease progress after treatment with pemetrexed and platinum-based chemotherapy. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and not have a history of severe autoimmune diseases or other conditions that could interfere with the study.

Inclusion Criteria

My blood clotting time is normal or managed with medication.

My cancer is a confirmed type of mesothelioma.

You have a specific amount of disease that can be measured using specific criteria for peritoneal or pleural mesothelioma.

Exclusion Criteria

I have been diagnosed with HIV.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I have a lung condition not caused by an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 24 months

24 months

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Every 8 weeks until disease progression, then every 12 weeks

Extension

Participants may receive up to 1 year of additional pembrolizumab therapy if they progress after stopping

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial is testing pembrolizumab, an antibody therapy targeting PD-1 proteins on immune cells to potentially enhance the body's ability to fight cancer. It includes laboratory biomarker analysis and pharmacogenomic studies to understand how genes affect a person's response to drugs.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 3 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible for up to 1 year of additional pembrolizumab therapy if they progress after stopping pembrolizumab.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

In a study involving 25 patients with PD-L1-positive malignant pleural mesothelioma, pembrolizumab demonstrated a 20% objective response rate, indicating potential anti-tumor activity in this aggressive cancer.

The treatment was generally well tolerated, with 64% of patients experiencing treatment-related adverse events, but no treatment-related deaths occurred, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Alley, EW., Lopez, J., Santoro, A., 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]

In the KEYNOTE-158 study involving 118 patients with previously treated malignant pleural mesothelioma (MPM), pembrolizumab demonstrated an 8% objective response rate, with a median duration of response of 14.3 months, indicating its potential efficacy as a treatment option regardless of PD-L1 status.

The treatment was associated with manageable safety, as 69% of patients experienced treatment-related adverse events, with serious events occurring in 12%, highlighting the need for careful monitoring but suggesting that pembrolizumab can be tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. Yap, TA., Nakagawa, K., Fujimoto, N., 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]

Citations

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jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2802254

Pembrolizumab Use Among Adults With Diffuse Malignant ...

In this cohort study of 24 patients with DMPM treated with pembrolizumab, we observed a partial response of 21% and stable disease of 53% as the best overall ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10942662/

Clinical Outcomes Associated With Pembrolizumab ...

In summary, these preliminary data suggest that pembrolizumab has clinical activity in DMPM. Furthermore, we observed potentially superior outcomes in patients ...

3.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-unresectable-advanced-or-metastatic-malignant-pleural

FDA approves pembrolizumab with chemotherapy for ...

The trial demonstrated a statistically significant improvement in OS for patients treated with pembrolizumab with chemotherapy compared to those ...

4.

merck.com

merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-versus-chemotherapy-alone-as-first-line-treatment-for-advanced-malignant-pleural-mesothelioma/

KEYTRUDA® (pembrolizumab) Plus Chemotherapy ...

KEYTRUDA plus chemotherapy showed a statistically significant and clinically meaningful improvement in OS compared to chemotherapy alone in these patients.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11894505/

Pembrolizumab as an effective treatment for diffuse malignant ...

This patient obtained significant clinical benefits from pembrolizumab, with disappearance of symptoms, a lasting stable disease response with a progression- ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28291584/

Clinical safety and activity of pembrolizumab in patients ...

Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8474198/

Retrospective Evaluation of the Use of Pembrolizumab in ...

We have presented real-world data on the safety and efficacy of pembrolizumab in mesothelioma from the largest patient cohort analyzed to date. We found that ...