Dupilumab_Metastatic NSCLC

NCT ID: NCT05013450

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-10
• Study Completion Date: 2025-12-09

Brief Summary

This is a multi cohort, sequential enrollment clinical trial to determine the safety and tolerability of Dupilumab and Anakinra with PD-(L)1 blockade for patients with relapsed/refractory metastatic NSCLC. For Phase 2, to determine the effect of adding IL-4Ra and IL-1R blockade to PD-(L)1 blocking agents in patients with relapsed/refractory NSCLC, who have progressed on prior PD-(L)1 agents.

Conditions

Metastatic Non-small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dupilumab + anti-PD-1/PD-L1 (SOC)

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 Type: EXPERIMENTAL

Dupilumab

Intervention Type: DRUG

three q3w cycles

PD-1/PD-L1 blockade

Intervention Type: DRUG

SOC immunotherapy with PD-1/PD-L1 blockade

Anakinra + Dupilumab + anti-PD-1/PD-L1 (SOC)

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

Group Type: EXPERIMENTAL

Dupilumab

Intervention Type: DRUG

three q3w cycles

PD-1/PD-L1 blockade

Intervention Type: DRUG

SOC immunotherapy with PD-1/PD-L1 blockade

Anakinra

Intervention Type: DRUG

100 mg daily injection for Three q3w cycles

Interventions

Dupilumab

three q3w cycles

Intervention Type: DRUG

PD-1/PD-L1 blockade

SOC immunotherapy with PD-1/PD-L1 blockade

Intervention Type: DRUG

Anakinra

100 mg daily injection for Three q3w cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must have a pathologically confirmed diagnosis of NSCLC
• Patients must have progressed (clinically or radiographically) on or following prior therapy with a PD-1 or PD-L1 targeted antibody
• Patients may have only 0 or 1 intervening lines of therapy from the prior PD-(L)1 blocking therapy
• Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the time points indicated in the Study Calendar.
• Patient must be willing and able to have core needle biopsies, or forceps biopsies if clinically feasible by (Goal 3-6 biopsies, final number to be determined by the interventionalist performing the procedure as safe) of tumor prior to initiation of dupilumab and at the on-treatment time point. Should patients undergo pre-treatment or on-treatment biopsy procedure, and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician
• Age ≥ 18 years.
• ECOG 0-2. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

• Patients who have had chemotherapy within 14 days from start of therapy.
• Palliative radiotherapy is permitted at any time, if deemed in the best interest of the patient.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with <350 CD4+ T cells/microliter in the peripheral blood. HIV testing is not required for patients with no known history of HIV.
• Has known active Hepatitis B (e.g., HBV detected by PCR or active Hepatitis C (e.g., HCV RNA [qualitative] is detected). Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
• Receipt of a live vaccine within 30 days of planned start of study medication
• Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)Principle investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.
• History of irAE in response to prior immunotherapy that has not improved to a Grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy
• 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.
• Patient has received Anakinra in the last 12 months (Cohort B).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Marron

OTHER

Sponsor Role: lead

Responsible Party

Thomas Marron

Director, Early Phase Trials Unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Thomas Marron, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Tisch Cancer Institute, Mount Sinai Hospital

New York, New York, United States

Countries

United States

References

LaMarche NM, Hegde S, Park MD, Maier BB, Troncoso L, Le Berichel J, Hamon P, Belabed M, Mattiuz R, Hennequin C, Chin T, Reid AM, Reyes-Torres I, Nemeth E, Zhang R, Olson OC, Doroshow DB, Rohs NC, Gomez JE, Veluswamy R, Hall N, Venturini N, Ginhoux F, Liu Z, Buckup M, Figueiredo I, Roudko V, Miyake K, Karasuyama H, Gonzalez-Kozlova E, Gnjatic S, Passegue E, Kim-Schulze S, Brown BD, Hirsch FR, Kim BS, Marron TU, Merad M. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature. 2024 Jan;625(7993):166-174. doi: 10.1038/s41586-023-06797-9. Epub 2023 Dec 6.

Reference Type: DERIVED

PMID: 38057662 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY-21-00907

Identifier Type: -

Identifier Source: org_study_id