Dupilumab + Immunotherapy for Non-Small Cell Lung Cancer

Overseen By Thomas Marron, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Thomas Marron

Must not be taking: Immunosuppressants, Steroids, Antivirals, others

Disqualifiers: Chemotherapy, Autoimmune disease, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with non-small cell lung cancer (NSCLC) that has returned or worsened after previous treatments. The goal is to assess the safety and tolerability of these treatments, specifically by adding Dupilumab (an immunotherapy drug) and Anakinra to existing immunotherapy targeting cancer-fighting proteins PD-1 and PD-L1. Ideal participants are those diagnosed with NSCLC whose cancer has progressed after receiving PD-1 or PD-L1 treatments. Participants should be comfortable providing blood samples and undergoing biopsy procedures. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had chemotherapy within 14 days of starting the trial, and you should not be on systemic steroid therapy or other immunosuppressive treatments within 7 days prior to the first dose, unless it's a stable dose of chronic steroids equivalent to ≤ 10mg prednisone. Please discuss your specific medications with the trial team.

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

Research shows that Dupilumab is generally well-tolerated by patients. Its approval for other conditions suggests relative safety. When combined with PD-1/PD-L1 blockers, studies indicate it can be effective when other treatments fail. Side effects are usually mild, such as skin reactions or slight tiredness.

For the combination of Anakinra, Dupilumab, and PD-1/PD-L1 blockers, evidence is still being gathered. Anakinra, used for other conditions, is known to be safe, with mainly mild side effects like redness at the injection site.

Overall, previous research suggests both treatment combinations are safe. However, ongoing studies will further clarify any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they introduce a fresh approach alongside standard immunotherapies like PD-1/PD-L1 blockers. Dupilumab, known for treating allergic conditions, is being explored for its potential to modulate the immune system in a way that enhances the effectiveness of cancer immunotherapy. Additionally, the combination of dupilumab with anakinra, an anti-inflammatory drug, is being tested to see if it can further improve outcomes by reducing inflammation linked to cancer progression. This innovative combination could lead to more effective and personalized treatment options for patients.

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

Research has shown that anti-PD-1/PD-L1 therapies have greatly improved the health of people with non-small cell lung cancer (NSCLC), particularly those with high levels of the protein PD-L1. These treatments can extend patients' lives. In this trial, some participants will receive Dupilumab alongside anti-PD-1/PD-L1 therapies to assess any additional benefits. Early indications suggest this combination might enhance the body's cancer-fighting ability. Although limited information exists on using Dupilumab for NSCLC, it could offer new hope for patients who haven't responded to other treatments. Another arm of this trial will examine the combination of Dupilumab, Anakinra, and anti-PD-1/PD-L1 therapies to further explore potential benefits. ^{6 7 8 9 10}

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?

Adults over 18 with advanced NSCLC who've seen their cancer worsen after treatment with PD-1 or PD-L1 inhibitors can join. They must be able to provide blood samples, undergo biopsies, and use contraception if of childbearing potential. Exclusions include those with certain immune conditions, recent vaccines or chemotherapy, uncontrolled illnesses, pregnancy, specific drug allergies, organ transplants, and some infections.

Inclusion Criteria

I can care for myself despite any long-term disabilities I may have.

My lung cancer diagnosis has been confirmed by a lab test.

I agree to use birth control during and for 3 months after the study if I can have children.

Exclusion Criteria

I do not have any severe illnesses that could interfere with the study.

You have had a bad reaction to any protein-based medications. The principal investigator thinks you might not be able to attend all the study visits or that the trial might not be good for your health.

I am not on high-dose steroids or immunosuppressants, or have been for over 4 weeks on a low dose (≤10mg prednisone).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three q3w cycles of Dupilumab and Anakinra with PD-1/PD-L1 blockade

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab
• PD-1/PD-L1 blockade

Trial Overview The trial is testing Dupilumab in combination with a PD-1/PD-L1 inhibitor for patients whose NSCLC has relapsed or is refractory after previous treatments. It's a single-arm study aiming to see if blocking IL-4Ra alongside PD-(L)1 improves outcomes.

How Is the Trial Designed?

Group I: Dupilumab + anti-PD-1/PD-L1 (SOC) Experimental Treatment 2 Interventions

Patients will continue SOC immunotherapy with PD-1/PD-L1 blockade following progression of disease, and three q3w cycles of dupilumab will be administered

Group II: Anakinra + Dupilumab + anti-PD-1/PD-L1 (SOC) Experimental Treatment 3 Interventions

Patients will continue SOC immunotherapy with PD-1/PD-L1 blockade following progression of disease, and three q3w cycles of dupilumab and anakinra will be administered

Dupilumab is already approved in United States, European Union for the following indications:

Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Who Is Running the Clinical Trial?

Thomas Marron

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

A 67-year-old male with lung squamous cell carcinoma developed myocarditis after receiving durvalumab, a PD-L1 inhibitor, highlighting the potential for serious cardiac side effects from this treatment.

The patient's myocarditis led to a significant decrease in heart function but improved rapidly with glucocorticoid therapy, suggesting that timely intervention can effectively manage this rare but severe adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma. Zhou, B., Li, M., Chen, T., et al.[2022]

PD-L1 checkpoint inhibitors, like durvalumab, have shown significant efficacy in treating various solid tumors, including lung cancer and breast cancer, by suppressing tumor growth and improving patient survival.

While PD-L1 therapy is generally safe, it can cause adverse reactions such as pneumonitis and colitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. Chen, M., Jiang, J., Chen, J., et al.[2023]

Durvalumab, an anti-PD-L1 monoclonal antibody, is being tested in a Phase II study for its feasibility and effectiveness in patients with early-stage non-small cell lung cancer (NSCLC) by administering three infusions before surgery.

The study aims to achieve a complete surgical resection rate of at least 85% and assess major pathological response, with a total of 81 patients required to determine if neoadjuvant immunotherapy can improve survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[IoNESCO trial: Immune neoajuvant therapy in early stage non-small cell lung cancer]. Mignard, X., Antoine, M., Moro-Sibilot, D., et al.[2019]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

In a study involving 62 patients with recurrent/metastatic head and neck squamous cell carcinoma, durvalumab showed manageable safety, with 98.4% experiencing adverse events, but no drug-related discontinuations or deaths.

The objective response rate was 6.5%, with a higher response of 15.0% in patients with PD-L1 expression ≥25%, indicating potential efficacy in a subset of patients, and median overall survival was 8.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Segal, NH., Ou, SI., Balmanoukian, A., et al.[2020]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., et al.[2022]

In a meta-analysis of 16 clinical trials involving 6208 patients with non-small cell lung cancer, the overall incidence of immune-related adverse events (irAEs) was found to be 22%, with a higher rate of severe irAEs (4%) associated with PD-1 inhibitors compared to PD-L1 inhibitors.

The most common organ-specific irAEs occurred in the endocrine system, skin, pulmonary tract, and gastrointestinal tract, with pneumonitis being the leading cause of death among the 14 patients (0.34%) who died due to irAEs, highlighting the importance of monitoring and managing these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis. Sun, X., Roudi, R., Dai, T., et al.[2020]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a phase 2 trial involving 444 patients with advanced non-small-cell lung cancer (NSCLC), durvalumab (an anti-PD-L1 treatment) showed a response rate of 30.9% in patients with ≥90% PD-L1 expression, indicating its potential efficacy in heavily pretreated cases.

The safety profile of durvalumab was consistent with other similar treatments, with 9% of patients experiencing grade 3 or 4 treatment-related adverse events, suggesting it is manageable and generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Garassino, MC., Cho, BC., Kim, JH., et al.[2022]

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