Pembrolizumab for Early-Stage Non-Small Cell Lung Cancer

Recruiting at 12 trial locations

Overseen By Allison Lipps

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Greg Durm, MD

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active malignancy, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 54 weeks

244 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pembrolizumab, a type of immunotherapy, can benefit individuals with early-stage non-small cell lung cancer (NSCLC) after surgery. Researchers seek to compare the effectiveness of pembrolizumab against simply observing the patient post-surgery. The trial is recruiting individuals who have undergone surgery to remove stage I NSCLC with a tumor size of 1 to 4 cm and have not received other treatments like chemotherapy or radiation for this cancer. Participants will either receive pembrolizumab every six weeks or be monitored without additional treatment to compare outcomes. As a Phase 2 trial, this research focuses on assessing pembrolizumab'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 chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before participating. It's best to discuss your specific medications with the trial team.

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

Research shows that pembrolizumab, the treatment under study, has been well-tolerated in past studies. In one study, when combined with chemotherapy for non-small cell lung cancer, pembrolizumab was safe and extended patient survival. Another study found that using pembrolizumab before and after surgery was safe and delayed cancer recurrence.

The FDA has already approved pembrolizumab for other uses, indicating a history of safety. While no treatment is without risks, evidence so far suggests that pembrolizumab is generally safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Pembrolizumab is unique because it leverages the body's immune system to fight early-stage non-small cell lung cancer. Unlike traditional chemotherapy that directly attacks cancer cells, pembrolizumab is an immunotherapy that blocks the PD-1 pathway, effectively reactivating T-cells to target and destroy cancer cells. Researchers are excited about this treatment because it offers a potentially more targeted and less toxic approach compared to conventional treatments, which often come with significant side effects. Additionally, pembrolizumab is administered once every six weeks, which is more convenient compared to the more frequent dosing schedules of some standard therapies.

What evidence suggests that Pembrolizumab might be an effective treatment for early-stage non-small cell lung cancer?

Research has shown that pembrolizumab effectively treats non-small cell lung cancer (NSCLC). For patients with NSCLC, pembrolizumab has demonstrated a strong response in reducing cancer and has extended the time patients live without the cancer worsening. In this trial, participants in Arm A will receive pembrolizumab to evaluate its effectiveness in early-stage NSCLC after surgery, while Arm B will involve observation only. Additionally, pembrolizumab is approved for use alone in treating certain types of NSCLC, particularly when tumors express a protein called PD-L1. These findings suggest that pembrolizumab could be a beneficial treatment option for early-stage NSCLC after surgery. ^{2 3 4 6 7}

Who Is on the Research Team?

Greg Durm

Principal Investigator

Indiana University Melvin and Bren Simon Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 who've had surgery to remove stage I NSCLC with tumors between 1-4 cm and are in good health can join. They must not be pregnant, breastfeeding, or planning to conceive soon. People with certain genetic mutations, previous cancer treatments, active infections like TB or hepatitis, other cancers within the last 3 years, severe allergies to pembrolizumab ingredients, recent live vaccines, autoimmune diseases needing treatment in the past two years or organ transplants cannot participate.

Inclusion Criteria

Patients must have undergone complete surgical resection of their stage I NSCLC between 4-12 weeks prior to registration and have negative surgical margins (R0). NOTE: Both squamous and non-squamous histologies are allowed into the study. Cancers with a histology of 'adenosquamous' are considered a type of adenocarcinoma and thus 'non-squamous histology'. NOTE: Staging will be according to the AJCC 8th edition. Pathological tumor size must be 1.0 - 4.0 cm in greatest dimension. NOTE: According to AJCC 8th edition, subjects with lepidic predominant adenocarcinoma should be staged based on their invasive tumor size and not their total tumor size (i.e., subjects with lepidic predominant tumors whose invasive tumor size is less than 1 cm are not eligible, even if their total tumor size is 1.0 cm or greater). Surgery for this lung cancer must be completed at least 28 days prior to registration. Must have either previous NGS and PD-L1 results available using the Dako 22C3 antibody or have archival tissue of surgical specimen from current diagnosis available to perform analyses. If prior PD-L1 results with Dako 22C3 antibody are not available from a CLIA-accredited laboratory, subjects must be able to provide 5 x 5µm unstained slides for prospective analysis to be used for stratification. If NGS results are not available, subjects must be able to provide at least 10 x 10µm unstained and 1 x 4µm H&E slides from current diagnosis for future NGS and/or other genetic analyses. Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.

I am not pregnant or breastfeeding, and if of childbearing age, I use effective birth control or practice abstinence.

I have been mostly active and able to carry on all pre-disease activities without restriction in the last 28 days.

Exclusion Criteria

I have not received a live vaccine within the last 30 days.

I have an active tuberculosis infection.

I have received chemotherapy, radiation, or immunotherapy for my lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-12 weeks

Treatment

Participants receive Pembrolizumab 400 mg every 6 weeks for 9 cycles or are under observation

54 weeks

9 visits (in-person)

Follow-up

Participants are monitored for disease-free survival and overall survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing if Pembrolizumab given every six weeks for nine cycles improves outcomes compared to just watching after surgery for lung cancer. Patients will be randomly assigned to either get the drug or go into observation. The groups are divided based on PD-L1 protein levels and tumor size.

How Is the Trial Designed?

Group I: Arm A- Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 400mg IV every 6 weeks x 9 cycles

Group II: Arm B - Observation Active Control 1 Intervention

Observation only

Who Is Running the Clinical Trial?

Greg Durm, MD

Lead Sponsor

Trials

4

Recruited

390+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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]

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]

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, 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 a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., 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, 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]

Citations

1. keytruda.com keytruda.com/non-small-cell-lung-cancer/clinical-trial-results/

Non–Small Cell Lung Cancer - Clinical Trial Results View the clinical trial results for this treatment option for certain people with non–small cell lung cancer.

2. 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. In first-line metastatic ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39904561/

Perioperative pembrolizumab in early-stage non-small cell ... Conclusions: Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS. Keywords: Biomarker; Immune Checkpoint ...

4. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with non⁠–⁠small cell lung cancer (NSCLC) expressing programmed death ligand ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03425643

NCT03425643 | Efficacy and Safety of Pembrolizumab (MK ... This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302983

Perioperative Pembrolizumab for Early-Stage Non–Small- ... Neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological ...