Pembrolizumab for Preventing Lung Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Lung diseases, Autoimmune, Infections, 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: 6

Duration: 12 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well pembrolizumab works in preventing lung cancer patients with stage I-II non-small cell lung cancer or high-risk pulmonary nodules. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the study drug. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like steroids or immunosuppressive drugs, you may need to adjust them as per the trial's exclusion criteria.

What data supports the idea that Pembrolizumab for Preventing Lung Cancer is an effective drug?

The available research shows that Pembrolizumab is effective for treating non-small cell lung cancer (NSCLC). In a study called KEYNOTE-024, patients with advanced NSCLC who had not been treated before and received Pembrolizumab lived longer compared to those who received chemotherapy. Another study, KEYNOTE-010, showed that patients who had already tried other treatments and then received Pembrolizumab also lived longer than those who received chemotherapy. These studies suggest that Pembrolizumab can help patients with NSCLC live longer and manage their disease better than traditional chemotherapy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug pembrolizumab for preventing lung cancer?

Pembrolizumab has been shown to improve survival rates in patients with advanced non-small cell lung cancer (NSCLC) when used as a treatment, especially in those whose tumors express a protein called PD-L1. It has been approved by the FDA for treating metastatic NSCLC, demonstrating significant improvements in survival compared to chemotherapy. ^{1 2 3 4 5}

What safety data is available for pembrolizumab in lung cancer treatment?

Pembrolizumab, also known as Keytruda or MK-3475, has been evaluated for safety in various studies. A phase II trial (NCT03197467) reported interim safety results for pembrolizumab as a neoadjuvant treatment in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors like pembrolizumab can cause adverse effects such as pneumonitis, occurring in 1%-5% of patients, and rare immune-related adverse events like type 1 diabetes mellitus in 0.2% of cases. The FDA approved pembrolizumab for metastatic NSCLC based on trials showing improved progression-free and overall survival compared to chemotherapy, indicating a favorable safety profile relative to traditional treatments. ^{1 2 4 6 7}

Is pembrolizumab generally safe for humans?

Pembrolizumab, also known as Keytruda, is generally considered less toxic than traditional chemotherapy, but it can cause some serious side effects. These include pneumonitis (inflammation of the lungs) in 1%-5% of patients and type 1 diabetes in 0.2% of cases. It's important to discuss potential risks with your doctor. ^{1 2 4 6 7}

Is the drug Pembrolizumab a promising treatment for preventing lung cancer?

Yes, Pembrolizumab is a promising drug for preventing lung cancer. It has shown positive results in improving survival rates for patients with non-small cell lung cancer, especially those with high PD-L1 expression. It is approved by the FDA for certain types of lung cancer and has demonstrated better outcomes compared to traditional chemotherapy. ^{1 2 4 8 9}

How is the drug pembrolizumab unique for preventing lung cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells. It is used before surgery in non-small cell lung cancer to improve outcomes, which is different from traditional chemotherapy approaches. ^{1 2 4 8 9}

Research Team

Jianjun Zhang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults who've had stage I-II non-small cell lung cancer treated curatively, or those with high-risk pulmonary nodules. They must have good blood counts, organ function, and be able to follow the study's contraception rules. Excluded are individuals with active autoimmune diseases, certain infections like hepatitis or tuberculosis, recent use of immunosuppressants or live vaccines, and women who are pregnant or breastfeeding.

Inclusion Criteria

I am not pregnant or breastfeeding and will follow birth control advice for 120 days due to treatment risks.

I have lung nodules found by CT scan but no history of lung cancer.

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

I have received treatment with specific medications before.

I had chest radiotherapy that affected the same area as my lung nodules.

I have an immune system disorder or have been on steroids recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously over 30 minutes on day 1, repeated every 3 weeks for up to 4 cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT scans and blood sample collection

6 months

2 visits (in-person)

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The IMPRINT-Lung Study is testing pembrolizumab's effectiveness in preventing lung cancer recurrence in patients post-treatment for early-stage disease or those at high risk due to pulmonary nodules. It involves monitoring through CT scans and quality-of-life assessments while receiving this immunotherapy drug that boosts the immune system against cancer cells.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 4 Interventions

Participants receive pembrolizumab IV over 30 minutes on day 1. Treatment repeat every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans and collection of blood samples throughout the trial.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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 (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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

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. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab Shows Promise for NSCLC. [2015]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]