What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC), particularly those involving PD-1/PD-L1 inhibitors and chemotherapy, are associated with a range of side effects. PD-1/PD-L1 inhibitors, such as pembrolizumab, nivolumab, and atezolizumab, can cause immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Chemotherapy agents, like platinum-based drugs and taxanes, often lead to side effects such as nausea, vomiting, hair loss, myelosuppression, neuropathy, and increased risk of infections. Combining these treatments can result in a higher incidence of severe adverse events, including grade 3-4 toxicities.

What prior FDA approvals exist?

Several drugs targeting the PD-1/PD-L1 pathway have received FDA approval for the treatment of Non-Small Cell Lung Cancer (NSCLC). Pembrolizumab, a PD-1 inhibitor, is approved for use alone or in combination with chemotherapy for patients with advanced NSCLC, particularly those with high PD-L1 expression. Atezolizumab, a PD-L1 inhibitor, is also approved for use in combination with chemotherapy for patients with advanced nonsquamous NSCLC. Cemiplimab, another PD-1 inhibitor, has shown improved overall survival and progression-free survival in patients with high PD-L1 expression. These approvals highlight the effectiveness of targeting the PD-1/PD-L1 pathway in NSCLC treatment.

What other types of research exist?

Promising alternatives to Dupilumab with PD-(L)1 blockade for NSCLC patients include: <ol> <li>Pembrolizumab combined with chemotherapy, which has shown improved overall survival and progression-free survival in the KEYNOTE-407 trial.</li> <li></li> </ol> Nivolumab, which has demonstrated efficacy in patients with brain metastases and advanced NSCLC. 3. Atezolizumab, particularly in combination with chemotherapy for patients with high PD-L1 expression. 4. Lorlatinib for patients with ALK-positive NSCLC, showing significant brain penetration and efficacy. 5. Osimertinib for patients with EGFR-mutated NSCLC, improving overall survival regardless of T790M status.

← Back to Search

Monoclonal Antibodies

Dupilumab + Immunotherapy for Non-Small Cell Lung Cancer

Phase 1 & 2

Recruiting

Led By Thomas Marron, MD, PhD

Research Sponsored by Thomas Marron

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a pathologically confirmed diagnosis of NSCLC

Age ≥ 18 years

Must not have

History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted

History of allogeneic hematopoietic cell transplantation or solid organ transplantation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests the safety and effectiveness of using Dupilumab with immune system boosters in patients with advanced lung cancer that has not responded to other treatments. Dupilumab blocks a growth signal, while these boosters help the immune system attack the cancer. Durvalumab is a treatment approved for patients with a specific type of lung cancer which has not progressed following certain chemotherapy treatments.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include allergic reactions to the protein-based therapy (Dupilumab), issues from immunosuppression like increased infection risk and possibly inflammation-related symptoms due to the immune system's heightened activity.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Select...

I am 18 years old or older.

Select...

My cancer has worsened after treatment with a PD-1 or PD-L1 inhibitor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a history of lung conditions or inflammation from cancer treatment, but not from radiation.

Select...

I have had a bone marrow or organ transplant.

Select...

I have not had chemotherapy in the last 14 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Limiting Toxicity (DLTs)

Overall Response Rate (ORR)

Secondary study objectives

Best overall response (BORR)

Duration of response (DOR)

Overall Survival (OS)

+1 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dupilumab + anti-PD-1/PD-L1 (SOC)Experimental Treatment2 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 Treatment3 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Anakinra

2016

Completed Phase 4

~1320

Dupilumab

FDA approved

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors such as PD-1/PD-L1 inhibitors and, in some cases, IL-4Ra blockade. PD-1/PD-L1 inhibitors, like pembrolizumab and nivolumab, work by blocking the interaction between PD-1 receptors on T-cells and PD-L1 on tumor cells, thereby enhancing the immune system's ability to attack cancer cells. Dupilumab, an IL-4Ra blocker, targets the IL-4 and IL-13 pathways, which are involved in immune regulation and inflammation. Combining IL-4Ra blockade with PD-(L)1 inhibitors may provide a synergistic effect, potentially improving the immune response against tumors. This is particularly important for NSCLC patients who have progressed on prior PD-(L)1 therapies, as it offers a new avenue for treatment and hope for better outcomes.

EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis.