Pembrolizumab for Preventing Lung Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pembrolizumab can prevent lung cancer from developing or returning in individuals with stage I-II non-small cell lung cancer or high-risk lung nodules. Pembrolizumab, a type of immunotherapy, boosts the body's immune system to combat cancer cells. The trial suits those who have had stage I-II lung cancer but are now cancer-free, or those with lung nodules at moderate to high risk of becoming cancerous, even without a biopsy-confirmed cancer diagnosis. Participants will receive pembrolizumab through an IV every three weeks for up to four cycles and will undergo regular CT scans and blood tests. As a Phase 2 trial, this research measures how well pembrolizumab works in an initial, smaller group of people.

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.

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

Research has shown that pembrolizumab has been studied for its safety in various types of cancer. In these studies, serious side effects occurred in about half of the patients who received the treatment, with 50.6% experiencing severe side effects. In some instances, these side effects were so severe that 12.7% of patients had to discontinue the treatment. Unfortunately, 5.9% of patients died due to these side effects, which can include issues caused by the immune system attacking healthy cells.

While these numbers might seem concerning, it's important to note that pembrolizumab is already approved for treating other cancers, indicating it has passed strict safety evaluations for those uses. This offers some reassurance about its safety. However, if considering joining a trial, discussing the potential risks and benefits with the study team or your doctor is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for lung cancer, which often include chemotherapy and radiation, pembrolizumab is unique because it harnesses the power of the immune system to fight cancer. Pembrolizumab is a type of immunotherapy known as a checkpoint inhibitor, which works by blocking the PD-1 pathway—a mechanism that tumors use to evade the immune system. This novel approach allows the body’s own defenses to better recognize and attack cancer cells. Researchers are excited about pembrolizumab because it offers the potential for more targeted treatment with potentially fewer side effects compared to conventional therapies.

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

Research has shown that pembrolizumab, a treatment that boosts the immune system, holds promise for treating lung cancer. Studies have found that pembrolizumab can improve survival rates for patients with advanced non-small cell lung cancer (NSCLC). For instance, some trials reported a five-year survival rate of up to 22% with this treatment. Pembrolizumab helps the immune system attack cancer cells, potentially preventing the cancer from growing and spreading. Overall, pembrolizumab has proven effective as a standard treatment for lung cancer in many cases. Participants in this trial will receive pembrolizumab to evaluate its potential in preventing lung cancer progression. ^{1 2 6 7 8}

Who Is on the Research Team?

Jianjun Zhang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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 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]

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]

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 (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]

Citations

1. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for previously untreated PD ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

4. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(24)00081-0/fulltext

5-Year Real-World Outcomes With Frontline ... With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9942927/

Effectiveness and safety of pembrolizumab for patients with ... Several randomized controlled trials (RCTs) have confirmed the favorable clinical benefit of pembrolizumab in advanced non-small cell lung cancer (NSCLC).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924000066

Safety profile of pembrolizumab monotherapy based on an ... Grade 3−5 AEs occurred in 50.6% of patients. AEs led to pembrolizumab discontinuation in 12.7% of patients and death in 5.9%. Immune-mediated AEs and infusion ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... The estimated 5-year OS rates were 11.9% and 7.4% in the pembrolizumab and chemotherapy groups, respectively (Data Supplement). Safety. In the ...