PCSK9 + PD-1 Inhibitors for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Duke University
Must not be taking: PCSK9 inhibitors
Disqualifiers: Cardiac issues, Uncontrolled diabetes, Recent surgery, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?PCSK9 mediates immune checkpoint blockade resistance by downregulating tumor cell surface MHC class 1 molecules. This study will evaluate if combining the anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab can generate anti-tumor activity and clinical responses in patients with metastatic lung cancer who have progressed on first line immune checkpoint blockade therapy.
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, you must have a minimum of 4 weeks since any other experimental anti-cancer therapies or prior PD-1 treatment before joining the study.
What data supports the effectiveness of the drug combination of PCSK9 and PD-1 inhibitors for non-small cell lung cancer?
Research shows that cemiplimab, a PD-1 inhibitor, significantly improves survival in patients with advanced non-small cell lung cancer with high PD-L1 expression compared to chemotherapy. This suggests that cemiplimab is effective in treating this type of lung cancer.
12345Is the combination of PCSK9 and PD-1 inhibitors safe for humans?
Cemiplimab, a PD-1 inhibitor, has been studied for safety in treating non-small cell lung cancer and cutaneous squamous cell carcinoma. Common side effects include fatigue, rash, and diarrhea, but it is generally considered safe for use in humans. However, specific safety data for the combination with PCSK9 inhibitors is not available.
23467What makes the drug combination of Alirocumab and Cemiplimab unique for treating non-small cell lung cancer?
This drug combination is unique because it combines Alirocumab, a PCSK9 inhibitor typically used for lowering cholesterol, with Cemiplimab, a PD-1 inhibitor used in immunotherapy for cancer. This novel approach targets both cholesterol metabolism and the immune system, potentially offering a new way to treat non-small cell lung cancer.
3891011Eligibility Criteria
This trial is for adults with advanced lung cancer that has worsened despite previous PD-1 inhibitor therapy. Participants must be in good physical condition, not have had major surgery recently, and their blood tests need to meet specific criteria. They can't join if they've used PCSK9 inhibitors before or have serious heart problems, uncontrolled diabetes, HIV/AIDS, another recent cancer diagnosis, or severe reactions to prior immunotherapy.Inclusion Criteria
Signed written informed consent
I am fully active or can carry out light work.
My NSCLC has specific genetic changes and has worsened despite targeted treatment.
+5 more
Exclusion Criteria
I have been treated with PCSK9 inhibitors before.
I do not have uncontrolled heart problems.
Your diabetes is not under control, as shown by a high HbA1c level.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a combination of anti-PCSK9 antibody alirocumab and anti-PD-1 antibody cemiplimab
Up to 110 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days post last dose
Participant Groups
The study is testing the combination of two drugs: Alirocumab (a cholesterol-lowering medication) and Cemiplimab (an immune system booster), to see if they work together against lung cancer that hasn't responded well to standard treatments. The goal is to find out whether this combo can shrink tumors in patients who haven't had luck with other therapies.
1Treatment groups
Experimental Treatment
Group I: Alirocumab and CemiplimabExperimental Treatment1 Intervention
Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab
Alirocumab is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Praluent for:
- High cholesterol - Familial Homozygous
- Cardiovascular Risk Reduction
- High cholesterol - Familial Heterozygous
- High Cholesterol
🇺🇸 Approved in United States as Praluent for:
- High cholesterol - Familial Homozygous
- Cardiovascular Risk Reduction
- High cholesterol - Familial Heterozygous
- Primary hyperlipidemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Duke UniversityDurham, NC
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Who Is Running the Clinical Trial?
Duke UniversityLead Sponsor
Regeneron PharmaceuticalsIndustry Sponsor
References
First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. [2023]Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.
Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50. [2022]Label="Background" NlmCategory="UNASSIGNED">For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020.
Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. [2022]We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.
Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. [2023]In metastatic non-small cell lung cancer (NSCLC), tumors that do not harbor driver mutations in EGFR or gene fusions in ALK and ROS, PD-1 and PD-L1 inhibitors have become a cornerstone in first line treatment, either as monotherapy or in combination with chemotherapy. This paper reviews cemiplimab-rwlc, the third PD-1/L1 inhibitor to be approved in the setting for first line treatment in NSCLC, as monotherapy or in combination therapy with chemotherapy, to provide a perspective on the subtle differences in patient population for the cemiplimab studies and consideration of its primary and subgroup results in the context of first line therapies for NSCLC.
Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]To systematically evaluate the efficacy and safety of pembrolizumab (PD-1/PD-L inhibitor) and adjuvant chemotherapy to treat NSCLC and provide evidence-based reference for clinical use.
Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.
Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. [2023]Patients with non-small-cell lung cancer (NSCLC) that is resistant to PD-1 and PD-L1 (PD[L]-1)-targeted therapy have poor outcomes. Studies suggest that radiotherapy could enhance antitumour immunity. Therefore, we investigated the potential benefit of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) inhibition alone or combined with radiotherapy.
Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: a meta analysis of randomized controlled trials. [2021]The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC).
Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. [2020]In the past decade novel agents are on the market for non-small cell lung cancer adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation is necessary in the everyday clinical practice for the oncologic patient. Immunotherapy is nowadays the novel therapy for advanced stage non-small cell lung cancer with two agents nivolumab and pembrolizumab. In the current case series we will present adverse effects from our centers and comment on the treatment and follow-up of the patients.
Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. [2020]In non-small cell lung cancer (NSCLC), the first immune checkpoint inhibitor to be approved by the US Food and Drug Administration was nivolumab, based on a survival advantage over docetaxel in recurrent squamous NSCLC, a difficult-to-treat histology. In addition, several other immune checkpoint inhibitors are also in late-stage development. Most of these agents inhibit the programmed cell death protein 1 (PD-1) pathway, targeting either the PD-1 receptor or its ligand, programmed cell death ligand 1 (PD-L1). In addition to nivolumab, pembrolizumab is a PD-1 inhibitor under investigation in NSCLC, and atezolizumab (MPDL3280A), durvalumab (MEDI4736), and avelumab (MSB0010718C) are PD-L1 inhibitors under investigation. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint inhibitors ipilimumab and tremelimumab are also under investigation in NSCLC, largely as part of combination approaches rather than as monotherapy. PD-L1 expression as a potential biomarker to select patients most likely to respond to inhibitors of the PD-1 pathway has been widely studied.
A case of dramatic reduction in cancer-associated thrombus following initiation of pembrolizumab in patient with a poor performance status and PD-L1+ lung adenocarcinoma harboring CCDC6-RET fusion gene and NF1/TP53 mutations. [2021]Pembrolizumab is a standard treatment for non-small cell lung cancer (NSCLC) with high-PD-L1 expression; however, its effect is dismal in patients with poor physical condition. Additionally, the effect of immunotherapy is generally limited in NSCLC harboring driver mutations such asEGFR, ALK, or RET gene aberrations.