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

Trial Summary

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 the combination of Dupilumab and Cemiplimab safe for early-stage lung cancer?

Cemiplimab has been studied for other cancers and has shown acceptable safety with low rates of treatment discontinuation and death. However, specific safety data for the combination of Dupilumab and Cemiplimab in early-stage lung cancer is not provided in the available research. ^{1 2 3 4 5}

How does the drug combination of Dupilumab and Cemiplimab differ from other treatments for early-stage lung cancer?

The combination of Dupilumab and Cemiplimab for early-stage lung cancer is unique because it involves the use of Cemiplimab, a PD-1 inhibitor, which has shown efficacy in advanced non-small cell lung cancer (NSCLC) as both monotherapy and in combination with chemotherapy. This approach may offer a novel mechanism of action by targeting the immune system to fight cancer cells, which is different from traditional chemotherapy that directly targets cancer cells. ^{2 3 4 6 7}

What is the purpose of this trial?

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 lung cancer (NSCLC). The study will include participants with a confirmed diagnosis of NSCLC who are deemed to be surgical candidates, or patients who have a smoking history and radiographic findings highly suggestive if a diagnosis of NSCLC who are scheduled to undergo diagnostic biopsy. On Day 1, participants will receive neoadjuvant therapy consisting of 600 mg of dupilumab (2 SC injections of 300 mg) and 350 mg of IV cemiplimab. Participants will undergo standard of care surgery, which will be scheduled within 7 days of Day 15. Participants will be followed up 30 days following administration of dupilumab and cemiplimab for adverse event (AE) and dose limiting toxicity (DLT) monitoring. Participants will be offered adjuvant therapy as per standard of care, outside the context of this clinical treatment, and undergo subsequent standard of care monitoring for recurrence. The study team will monitor the status of the participant through chart review, or by telephone should the patient not continue to follow with a physician at Mount Sinai, for up to 5 years.

Research Team

Thomas Marron, MD PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

4. 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]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

6. United States 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. [2023]

7. 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]