Pembrolizumab for Early-Stage Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+12 other locations
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.12345
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.34567
How is the drug pembrolizumab unique for treating early-stage non-small cell lung cancer?
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.
See 2 more
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.
See 16 more
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 OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A- PembrolizumabExperimental Treatment1 Intervention
Pembrolizumab 400mg IV every 6 weeks x 9 cycles
Group II: Arm B - ObservationActive Control1 Intervention
Observation only
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Virginia Commonwealth UniversityRichmond, VA
Moffit Cancer CenterTampa, FL
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
University of Nebraska Medical CenterOmaha, NE
More Trial Locations
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Who Is Running the Clinical Trial?
Greg Durm, MDLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Pembrolizumab Shows Promise for NSCLC. [2015]Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020]Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.