Pembrolizumab for Early-Stage Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+12 other locations

Overseen by Greg Durm

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Greg Durm, MD

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active malignancy, Autoimmune disease, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

A randomized trial of adjuvant Pembrolizumab following surgical resection versus observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm. Patients will be randomized (1:1) 4-12 weeks following surgery to either: * Arm A: Pembrolizumab 400 mg every 6 weeks × 9 cycles * Arm B: Observation Stratification factors will include: PD-L1 TPS (\<50% vs. ≥50%), and tumor size (1-2 cm vs. \>2-4 cm)

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.

What data supports the effectiveness of the drug pembrolizumab for early-stage non-small cell lung cancer?

Pembrolizumab has shown promise in treating non-small cell lung cancer (NSCLC) by improving survival rates in patients with advanced stages of the disease, as seen in trials like KEYNOTE-024 and KEYNOTE-010. Additionally, early-phase trials and studies have indicated that pembrolizumab is effective and well-tolerated in various solid tumors, including NSCLC. ^{1 2 3 4 5}

Is pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (Keytruda) has been used in various clinical trials and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects like pneumonitis (lung inflammation) can occur in a small percentage of patients. ^{3 4 5 6 7}

How is the drug pembrolizumab unique for treating early-stage non-small cell lung cancer?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking a protein called PD-1, which helps the immune system attack cancer cells. Unlike traditional chemotherapy, it is used before surgery to potentially shrink tumors in early-stage non-small cell lung cancer. ^{2 3 4 5 8}

Research Team

Greg Durm

Principal Investigator

Indiana University Melvin and Bren Simon Cancer Center

Eligibility Criteria

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 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Pembrolizumab (PD-1 Inhibitor)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Virginia Commonwealth University Richmond, VA

Moffit Cancer Center Tampa, FL

Rutgers Cancer Institute of New Jersey New Brunswick, NJ

University of Nebraska Medical Center Omaha, NE

More Trial Locations

Who Is Running the Clinical Trial?

Greg Durm, MD

Lead Sponsor

Trials

4

Patients Recruited

390+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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]

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]

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 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]

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 (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]

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]

References

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

Pembrolizumab Shows Promise for NSCLC. [2015]

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

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

3. 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]

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

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

5. 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]

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

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

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020]