Cemiplimab + Dupilumab for Lung Cancer

(Dupi-Cemi Trial)

Overseen By Antoine Desilets, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Immunomodulatory drugs, Immunosuppressive drugs

Disqualifiers: Autoimmune disorders, Metastatic disease, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using immunomodulatory drugs, including dupilumab, within 2 months before starting treatment. You also need to stop using immunosuppressive drugs or systemic steroids 7 days before treatment, except for chronic steroids at low doses.

What data supports the effectiveness of the drug Cemiplimab + Dupilumab for lung cancer?

Cemiplimab has shown significant survival benefits in patients with advanced non-small-cell lung cancer (NSCLC) with high PD-L1 expression, improving overall survival and progression-free survival compared to chemotherapy. It is also approved for treating advanced cutaneous squamous cell carcinoma, indicating its effectiveness in enhancing the immune system's response to tumors. ^{1 2 3 4 5}

What is the purpose of this trial?

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-stage, resectable NSCLC. Phase 1b focuses on safety and feasibility, using a 3+3 design to monitor dose-limiting toxicities (DLTs), while Phase 2a assesses the major pathological response (MPR) rate with a Simon's two-stage minimax design. Secondary endpoints include event-free survival, overall survival, and translational objectives such as deep immune monitoring from patient samples, with the trial expected to enroll 24 patients at CHUM over five years.

Research Team

Antoine Desilets, MD, MSc

Principal Investigator

CHUM

Eligibility Criteria

This trial is for people with early-stage, operable non-small cell lung cancer (NSCLC). Participants should be eligible for surgery to remove the tumor and must not have received prior systemic therapy for NSCLC. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

My lung cancer diagnosis was confirmed with a tissue sample.

I agree to have at least 3 needle biopsies as advised by my doctor.

A team of doctors has approved me for surgery to remove my tumor.

Exclusion Criteria

I haven't needed systemic treatment for an autoimmune disease in the last year, except for hormone replacements like insulin or thyroxine.

HIV infection with detectable viral load or not on a stable HAART regimen

Active Hepatitis B or C (PCR-detectable)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Participants receive neoadjuvant cemiplimab and dupilumab to assess safety and feasibility using a 3+3 design to monitor dose-limiting toxicities

4 weeks

Weekly visits for monitoring

Phase 2a Treatment

Participants continue treatment to assess major pathological response (MPR) rate with a Simon's two-stage minimax design

Until day of surgery

Regular visits until surgery

Follow-up

Participants are monitored for safety, event-free survival, and overall survival after treatment and surgery

Up to 5 years

Periodic visits for long-term monitoring

Treatment Details

Interventions

• Cemiplimab
• Dupilumab

Trial Overview The study tests combining two drugs, Cemiplimab (anti-PD-1) and Dupilumab (anti-IL-4Rα), before surgery in NSCLC patients. It's checking if this combo is safe (Phase 1b) and effective at causing a major response in the tumor tissue (Phase 2a).

Participant Groups

Group I: Neoadjuvant cemiplimab and dupilumab combination therapy Experimental Treatment 2 Interventions

Neoadjuvant immunotherapy administered prior to thoracic surgery

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

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 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]

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]

References

1. 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]

2. 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]

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

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

5. 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]