Alirocumab + Chemo for Lung Cancer

Overseen By Monika Anand, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: EGFR mutations, Active TB, Autoimmune, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

126 Participants Needed

Trial Summary

What is the purpose of this trial?

In this open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) will receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. Eligible patients will be randomized with equal allocation to two treatment groups. Permuted block randomization algorithm will be used for treatment assignment with stratification factors: stage (1B, 2A, 2B, 3A), and performance status (0 vs. 1). The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving other anti-tumor therapies or have used an anti-PCSK9 agent within 90 days of the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Alirocumab and Cemiplimab 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 alone. This suggests that cemiplimab can be effective in treating lung cancer, especially when used in combination with other treatments. ^{1 2 3 4 5}

Is the combination of Alirocumab and chemotherapy safe for treating lung cancer?

Cemiplimab, a drug similar to Alirocumab, has been studied for safety in treating various cancers, including lung cancer. Common side effects include immune-related reactions, but it is generally considered safe when used under medical supervision. ^{1 3 6 7 8}

How is the drug combination of Alirocumab and Cemiplimab with chemotherapy unique for treating lung cancer?

The combination of Alirocumab and Cemiplimab with chemotherapy is unique because Cemiplimab is a PD-1 inhibitor that enhances the immune system's ability to fight cancer, and it has shown significant survival benefits in patients with high PD-L1 expression in non-small cell lung cancer. This approach leverages the immune system in a novel way compared to traditional chemotherapy alone. ^{1 3 6 7 9}

Research Team

Neal Ready, MD, PhD

Principal Investigator

Duke University

Eligibility Criteria

Adults over 18 with a certain stage of lung cancer (NSCLC) that hasn't been treated yet. They must have a tumor at least 3 cm big, be in good physical shape, and considered able to undergo surgery. People who've had other cancers within the last two years or previous treatments for their lung cancer can't join.

Inclusion Criteria

I am 18 years old or older.

I am fully active or can carry out light work.

I am considered fit for surgery.

Exclusion Criteria

I have a history of lung inflammation not caused by an infection.

I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last week.

Hypersensitivity to alirocumab or any of its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery

9 weeks

3 visits (in-person)

Surgery

Surgical resection of the tumor following neoadjuvant therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Alirocumab
• Cemiplimab

Trial Overview The trial is testing if adding Alirocumab to standard chemo and Cemiplimab before surgery helps more than just chemo and Cemiplimab alone in patients with NSCLC. Participants are randomly placed into one of the two groups to compare results.

Participant Groups

Group I: Arm B Experimental Treatment 2 Interventions

Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles without alirocumab (PCSK9 inhibitor) prior to surgery

Group II: Arm A Experimental Treatment 3 Interventions

Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles with alirocumab (PCSK9 inhibitor) every 4 weeks prior to surgery

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

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

Findings from Research

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]

In the EMPOWER-Lung 1 trial, cemiplimab significantly improved overall survival compared to platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression (≥50%).

Patients receiving cemiplimab reported better quality of life and functioning, with a lower risk of definitive deterioration in symptoms such as dyspnea, cough, and fatigue, indicating that cemiplimab not only extends survival but also enhances the patient's overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. Gümüş, M., Chen, CI., Ivanescu, C., et al.[2023]

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]

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]

In the EMPOWER-Lung 3 study, patients with advanced non-small cell lung cancer (NSCLC) treated with cemiplimab plus chemotherapy had a median overall survival of 21.1 months compared to 12.9 months for those receiving chemotherapy alone, demonstrating a significant survival benefit after 28.4 months of follow-up.

Cemiplimab plus chemotherapy also resulted in improved progression-free survival (8.2 months vs. 5.5 months) and higher objective response rates (43.6% vs. 22.1%), although it was associated with a higher incidence of severe adverse events (48.7% vs. 32.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial. Makharadze, T., Gogishvili, M., Melkadze, T., et al.[2023]

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]

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, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).

The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]

References

1. England 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. [2022]

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

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. [2023]

3. New Zealand 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. [2023]

4. England 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. [2023]

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

Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial. [2023]

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

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

7. England 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. [2022]

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

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. [2021]

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

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. [2021]