Pembrolizumab + Radiation for Mesothelioma

Recruiting at 7 trial locations

Overseen By Charles Simone, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active infections, 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: Unknown

Duration: 6 months

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining IMPRINT (a type of radiation therapy) with pembrolizumab is a safe and effective treatment for malignant pleural mesothelioma (MPM), a cancer affecting the lung lining. Researchers seek to identify the highest dose of IMPRINT that results in only mild side effects when used with pembrolizumab. The trial seeks participants with MPM that cannot be surgically removed and who have undergone at least one previous treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial.

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

Research has shown that pembrolizumab, when combined with radiation therapy, is generally safe for people with malignant pleural mesothelioma (MPM). One study found that pembrolizumab has an acceptable safety profile after radiation treatment for MPM, with side effects mostly mild or manageable. However, this is a Phase 1 trial, primarily focused on assessing the treatment's safety, so some unknown risks may remain. Patients should always discuss expectations with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the body's immune system to fight cancer cells, unlike traditional chemotherapy treatments for malignant pleural mesothelioma (MPM), which directly target and kill rapidly dividing cells. This drug is a type of immunotherapy known as a checkpoint inhibitor, which specifically blocks the PD-1 pathway, a mechanism that tumors use to hide from the immune system. Researchers are excited because, by unleashing the immune system on the cancer, pembrolizumab has the potential to offer a more targeted approach with possibly fewer side effects and could improve outcomes for patients with this challenging condition.

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

Research has shown that pembrolizumab can help treat malignant pleural mesothelioma (MPM). Studies have found that combining pembrolizumab with chemotherapy extends patient survival compared to chemotherapy alone. Pembrolizumab aids the immune system in fighting cancer by blocking a protein that typically prevents immune cells from attacking cancer cells. This trial combines pembrolizumab with radiation to explore its potential benefits for MPM. Although the combination with radiation is still under investigation, early results suggest it might be beneficial. Further research is underway to confirm these findings. ^{2 3 4 5 6}

Who Is on the Research Team?

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with malignant pleural mesothelioma who've had at least one prior systemic therapy. They must not be pregnant, agree to use contraception, and have certain lung function levels (DLCO >40%, FEV1 >50%). Exclusions include recent participation in other trials, specific treatments or vaccines within the last month, certain medical conditions including active infections or pneumonitis, and known hypersensitivity to pembrolizumab.

Inclusion Criteria

I agree to use contraception for the duration of the treatment and up to 150 days after, if required.

I am not pregnant or breastfeeding and will follow birth control advice for 4 months during and after treatment.

My doctor says my lung condition can't be treated with surgery.

Exclusion Criteria

I do not have any serious infections, other cancers, or major illnesses.

I have another cancer that hasn't needed treatment in the last 2 years.

My cancer is too large in a specific area to allow for certain treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the Maximum Tolerated Dose (MTD) of IMPRINT among the three candidate doses using a modified Continuous Reassessment Method (CRM)

6 months

Treatment

Participants receive pembrolizumab in combination with the determined safe dose of IMPRINT

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IMPRINT
• Pembrolizumab

Trial Overview The study tests IMPRINT combined with pembrolizumab to determine a safe dosage and its effectiveness against mesothelioma. Participants will first help find the highest dose of IMPRINT that's tolerable when used with pembrolizumab before it's tested as a potential treatment option.

How Is the Trial Designed?

Group I: Participants with malignant pleural mesothelioma (MPM) Experimental Treatment 2 Interventions

Participants will be diagnosed with malignant pleural mesothelioma and be deemed unresectable per thoracic surgeon assessment

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, can induce severe radiation recall pneumonitis in patients who have previously received radiation therapy, even after the initial radiation pneumonitis has resolved.

This case highlights the potential risk of radiation recall reactions associated with immune checkpoint inhibitors, which have been less commonly reported compared to reactions from traditional cytotoxic anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Radiation Recall Pneumonitis After the Resolution of Typical Asymptomatic Radiation Pneumonitis. Itamura, H., Ohguri, T., Yahara, K., 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]

The combination of the anti-PD-L1 antibody avelumab with stereotactic body radiation therapy (SBRT) was found to be tolerable in patients with malignant pleural mesothelioma, with no severe (grade 4 or 5) adverse events reported during the study.

Out of 13 patients, the most common side effects included mild to moderate reactions such as infusion-related allergic reactions and fatigue, indicating that while there are some adverse effects, they are manageable and do not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma. Rimner, A., Adusumilli, PS., Offin, MD., et al.[2023]

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 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]

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, 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 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]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04897022

NCT04897022 | A Study of Pembrolizumab and Radiation ... The purpose of this study is to find out whether IMPRINT in combination with pembrolizumab is a safe treatment for people with malignant pleural ...

3. 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 ... Malignant pleural mesothelioma often progresses rapidly, and the five-year survival rate is only 12%. Although incidence of malignant ...

4. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2025/PC0387-Keytruda-Mesothelioma_FINAL_Rec.pdf

Pembrolizumab (Keytruda) Malignant peritoneal mesothelioma is not currently an approved indication for pembrolizumab ... treatment comparison; MPM = malignant pleural mesothelioma; OS = ...

5. 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 ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03516-6/fulltext

1915P Phase I trial of adjuvant pembrolizumab after ... Pembrolizumab is well-tolerated after RT for MPM with acceptable safety profile. The study seems to suggest no difference in outcomes with extensive ...