Dupilumab + Cemiplimab for Early-Stage Lung Cancer

Overseen By Katherine Vandris

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Immunomodulators, Steroids

Disqualifiers: Autoimmune disorder, Metastatic disease, Active infection, 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)

Compensation: Varies

Number of Visits: 1

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with early-stage non-small cell lung cancer (NSCLC), using dupilumab and cemiplimab (an immunotherapy drug). The focus is on patients whose cancer remains at a stage where surgery could help. Participants will first receive this medication combination and then undergo surgery to remove the tumor. Individuals with a history of smoking, signs of this type of lung cancer, and who are surgical candidates might be a good fit for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used an immunomodulatory drug like dupilumab within 8 weeks before starting the trial or if you are on certain immunosuppressive therapies.

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

Research has shown that the combination of dupilumab and cemiplimab is generally safe for people. In earlier studies, patients taking these drugs experienced manageable side effects. Dupilumab, which targets a specific part of the immune system, has been used for other conditions and is known to be safe. Common side effects include mild skin reactions and eye problems. Cemiplimab, which boosts the immune system, might cause tiredness or a rash in some people. Serious side effects are rare for both drugs.

These studies suggest that while some side effects may occur, they are usually mild or moderate. Researchers continue to study this combined treatment to ensure its safety and effectiveness. Clinical trial participants are closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Dupilumab and Cemiplimab for early-stage non-small-cell lung cancer (NSCLC) because this approach targets the immune system differently from standard treatments like chemotherapy or targeted therapy. Dupilumab is an antibody that blocks certain pathways involved in inflammation, while Cemiplimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination could potentially enhance the body's ability to fight cancer more effectively, offering a novel option beyond traditional therapies. Additionally, the use of subcutaneous Dupilumab may provide a more convenient administration method compared to some existing treatments.

What evidence suggests that this trial's treatments could be effective for early-stage lung cancer?

In this trial, participants with early-stage non-small cell lung cancer (NSCLC) will receive a combination of cemiplimab and dupilumab. Research has shown that cemiplimab, a treatment that enhances the immune system, can improve the body's ability to detect and destroy cancer cells in NSCLC. Studies have found that combining cemiplimab with chemotherapy can significantly benefit patients. Dupilumab, another treatment in this trial, reduces inflammation, potentially enhancing the effectiveness of cancer treatments. Early studies combining dupilumab and cemiplimab in early-stage NSCLC have assessed their safety and practicality, yielding promising results. These treatments aim to strengthen the body's natural defenses, potentially leading to better cancer control. ^{1 2 3 4 6}

Who Is on the Research Team?

Thomas Marron, MD PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with early-stage, resectable non-small cell lung cancer (NSCLC). Candidates must have a confirmed NSCLC diagnosis or strong indications of NSCLC and be scheduled for biopsy. They should be able to undergo surgery, provide blood samples, and agree to use contraception. People who are pregnant, breastfeeding, or unable to consent are excluded.

Inclusion Criteria

The participant must be amenable and capable of providing blood samples (6 heparinized tubes, 2 streck tubes, approx

You possess the requisite system/laboratory value.

I am mostly active and can care for myself, despite any long-term disabilities like cerebral palsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with 600 mg of dupilumab and 350 mg of cemiplimab

2 weeks

1 visit (in-person)

Surgery

Participants undergo standard of care surgery for early-stage, resectable NSCLC

Within 7 days of Day 15

Follow-up

Participants are monitored for adverse events and dose limiting toxicities for 30 days post-treatment

30 days

Long-term Follow-up

Participants are monitored for recurrence and overall survival through chart review or telephone for up to 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Dupilumab

Trial Overview The study tests neoadjuvant therapy using Dupilumab and Cemiplimab in patients with early-stage NSCLC before they undergo surgery. Participants will receive injections of Dupilumab and an IV of Cemiplimab followed by standard surgery within two weeks after treatment initiation.

How Is the Trial Designed?

Group I: Non-small-cell lung cancer (NSCLC) Experimental Treatment 2 Interventions

Participants will receive neoadjuvant subcutaneous Dupilumab 600mg and intravenous Cemiplimab 350mg on Day 1. Participants will proceed to standard of care surgery for early-stage, resectable NSCLC (within 7 days of Day 15), and will be observed for adverse events and dose limiting toxicities.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[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]

In the EMPOWER-Lung 3 study involving 466 patients with advanced non-small cell lung cancer (aNSCLC), cemiplimab combined with chemotherapy significantly improved overall survival (OS) to 21.9 months compared to 13.0 months with placebo, demonstrating its efficacy as a first-line treatment.

While cemiplimab plus chemotherapy showed better survival outcomes, it also resulted in a higher incidence of grade ≥3 adverse events (43.6%) compared to placebo plus chemotherapy (31.4%), indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Gogishvili, M., Melkadze, T., Makharadze, T., 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 is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[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]

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]

Citations

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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 ...

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Phase I/​II Study of Neoadjuvant Cemiplimab and ... This phase 1b/2a study evaluates the safety, feasibility, and efficacy of combining dupilumab (anti-IL-4Rα) and cemiplimab (anti-PD-1) in patients with early- ...

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Dupilumab and Cemiplimab for the Treatment of Early- ... This phase I/II trial tests the safety and efficacy of dupilumab and cemiplimab in treating patients with early stage non-small cell lung cancer that can be ...

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Predictive value of machine learning for PD-L1 expression ... At present, radiomics- or pathomics-based ML methods are applied for the prediction of PD-L1 expression in NSCLC, which both achieve satisfactory accuracy.

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Neoadjuvant Dupilumab and Cemiplimab in Patients With ... This is a phase 1/2 study of combined treatment with dupilumab (anti-IL-4Ra) and cemiplimab (anti-PD-1) in patients with early-stage, resectable non-small cell ...