PCSK9 + PD-1 Inhibitors for Non-Small Cell Lung Cancer

Not currently recruiting at 1 trial location

Overseen By Scott Antonia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: PCSK9 inhibitors

Disqualifiers: Cardiac issues, Uncontrolled diabetes, Recent surgery, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 110 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with advanced non-small cell lung cancer that has spread and not responded to initial immune therapy. The study tests two drugs, alirocumab (a PCSK9 inhibitor) and cemiplimab (a PD-1 inhibitor), to determine if they work together more effectively against cancer. It suits those whose lung cancer has progressed despite previous treatments and whose disease can be measured by standard criteria. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from potentially effective new therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of alirocumab and cemiplimab is under study for safety in treating non-small cell lung cancer. Alirocumab aids the immune system in recognizing cancer cells, while cemiplimab assists in attacking them. Both have undergone testing in other studies.

Studies have found that cemiplimab, when combined with chemotherapy, improved survival in patients with advanced lung cancer, suggesting it is generally well-tolerated. Cemiplimab has been part of treatments with established safety records in cancer therapy.

Alirocumab has been used in other trials to enhance the immune system's ability to detect tumor cells. While specific safety data for this combination is still being collected, these treatments have been involved in other studies without major safety concerns.

The trial is in Phase 2, indicating that the treatment has passed initial safety testing. This phase examines how well patients tolerate the combination. Participants should always discuss potential risks with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of alirocumab and cemiplimab for non-small cell lung cancer because it targets cancer in a new way. Unlike traditional treatments like chemotherapy and radiation, which attack cancer cells directly, this combination leverages the body's immune system. Alirocumab is an anti-PCSK9 antibody that might enhance immune responses by affecting cholesterol metabolism, while cemiplimab, an anti-PD-1 antibody, helps unleash the immune system to recognize and destroy cancer cells. This dual approach could potentially improve outcomes by both boosting the immune attack and targeting cancer cells more effectively.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that cemiplimab, a medicine that helps the immune system fight cancer, can nearly double the average survival time for patients with non-small cell lung cancer. It also significantly reduces the risk of death or cancer progression. Studies have found that combining cemiplimab with chemotherapy extends patient survival compared to chemotherapy alone. In this trial, participants will receive a combination of cemiplimab and alirocumab. Alirocumab may enhance the immune system's ability to recognize cancer cells, potentially improving the effectiveness of treatments like cemiplimab. Early results suggest that using these two treatments together might help the body fight cancer more effectively in patients who haven't responded to initial treatments. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Alirocumab
• Cemiplimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Alirocumab and Cemiplimab Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

In patients with advanced non-small-cell lung cancer (NSCLC) and high PD-L1 expression (≥50%), cemiplimab showed significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared to pembrolizumab, based on a systematic review and network meta-analysis of randomized-controlled trials.

Cemiplimab demonstrated comparable overall survival (OS) and similar safety profiles to pembrolizumab, indicating it is a viable first-line treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Freemantle, N., Xu, Y., Wilson, FR., et al.[2022]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

In a phase 2 trial involving 90 patients with non-small-cell lung cancer resistant to PD-1/PD-L1 therapy, the combination of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) with radiotherapy did not show improved overall response rates compared to the therapy alone, leading to the trial's early termination due to futility.

The most common serious adverse events were manageable, but one patient in the low-dose radiotherapy group died from respiratory failure potentially related to the treatment, highlighting the need for careful monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schoenfeld, JD., Giobbie-Hurder, A., Ranasinghe, S., et al.[2023]

Recent advancements in pharmacogenomics have led to the development of novel agents for treating non-small cell lung cancer adenocarcinoma, emphasizing the importance of testing for specific mutations like EGFR and ALK in clinical practice.

Immunotherapy, particularly with agents like nivolumab and pembrolizumab, has emerged as a promising treatment for advanced non-small cell lung cancer, although monitoring for adverse effects is crucial during patient follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. Zarogoulidis, P., Chinelis, P., Athanasiadou, A., et al.[2020]

Pembrolizumab, a treatment for non-small cell lung cancer (NSCLC), showed beneficial effects in a patient with poor physical condition and specific genetic mutations (CCDC6-RET fusion and NF1/TP53 mutations), despite the general limitations of immunotherapy in such cases.

The study suggests that co-occurring NF1/TP53 mutations may serve as a positive predictive biomarker for the effectiveness of pembrolizumab in NSCLC patients with RET fusion genes, indicating a potential area for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Nakasuka, T., Ohashi, K., Watanabe, H., et al.[2021]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

At 35 months of follow-up, patients with advanced non-small-cell lung cancer and high PD-L1 expression treated with cemiplimab had a median overall survival of 26.1 months, significantly better than the 13.3 months for those receiving chemotherapy, indicating a strong survival benefit from cemiplimab.

The addition of chemotherapy to cemiplimab after disease progression resulted in a median overall survival of 15.1 months, suggesting that this combination could be an effective second-line treatment option for patients with advanced non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Özgüroğlu, M., Kilickap, S., Sezer, A., et al.[2023]

Nivolumab was the first immune checkpoint inhibitor approved for non-small cell lung cancer (NSCLC) by the FDA, showing a survival advantage over the traditional treatment docetaxel in recurrent squamous NSCLC, which is known to be challenging to treat.

Several other immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway are in late-stage development, with ongoing research into their efficacy and the potential use of PD-L1 expression as a biomarker to identify patients who are most likely to benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. Garon, EB.[2020]

PD-1/PD-L1 inhibitors, especially when combined with chemotherapy, significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC), with a hazard ratio of 0.74 indicating a strong benefit.

While PD-1/PD-L1 inhibitors alone do not enhance progression-free survival, combination therapy does, and it is associated with increased adverse events, particularly in patients receiving PD-1 inhibitors compared to PD-L1 inhibitors, which have a lower incidence of treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Li, ZQ., Yan, HC., Gu, JJ., et al.[2021]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

Citations

1. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06385262

NCT06385262 | TOP 2301: Neoadjuvant Chemo for NSCLC The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03740

Alirocumab in Combination with Cemiplimab for the ... This phase II trial tests the safety and effectiveness of alirocumab (a PCSK9 inhibitor) in combination with cemiplimab (a PD-1 inhibitor) in treating patients ...

4. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-demonstrates-durable-survival-benefit-five

Libtayo® (cemiplimab) Demonstrates Durable Survival ... Late-breaking data at WCLC show Libtayo monotherapy nearly doubled median overall survival and reduced the risks of death and disease progression by 41% and 50 ...

5. withpower.com withpower.com/trial/phase-2-lung-neoplasms-6-2024-526ae

Alirocumab + Chemo for Lung Cancer Research shows that cemiplimab, when combined with chemotherapy, improved survival in patients with advanced non-small cell lung cancer compared to chemotherapy ...

6. news.sanofi.us news.sanofi.us/2020-09-03-Late-breaking-Libtayo-R-cemiplimab-pivotal-data-in-advanced-non-small-cell-lung-cancer-and-basal-cell-carcinoma-to-be-presented-at-ESMO

Late-breaking Libtayo® (cemiplimab) pivotal data in ... "These trial outcomes highlight the potential of Libtayo to advance treatment of non-small cell lung cancer and basal cell carcinoma, and will ...