Neoadjuvant Dupilumab and Cemiplimab in Patients With Early-stage Resectable NSCLC
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06088771
- Lead Sponsor
- Icahn School of Medicine at Mount Sinai
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 21
Not provided
- Patients with history of autoimmune disorder or any patient who has used an immunomodulatory drug, such as dupilumab, within 8 weeks of starting treatment.
- Patients without any smoking history, or any patient for whom we already have tissue or ctDNA evidence of an activating EGFR mutation or an ALK or ROS1 rearrangement.
- Patients who have had chemotherapy or radiotherapy within 4 months prior to entering the study for a different primary tumor, nor can they have received locoregional therapy (e.g. radiation) for the target lesion that will be biopsied and subsequently resected. Previous therapy for a different cancer (a different primary) is acceptable.
- Patients may not be receiving any other investigational agents.
- Patients with metastatic disease, for whom the intent of surgery would not be curative.
- 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, as determined the treating investigator.
- Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- Use of another immunomodulatory drug, including dupilumab, that may confound interpretation of clinical and biospecimen analysis, within 8 weeks of enrollment.
- Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the administration of trial treatment. Patients on chronic steroids 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 known additional malignancy that is progressing and requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA, and breast cancer whom have been treated with curative intent, who may be on hormonal therapy.
- 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.
- Has known active Hepatitis B (e.g., HBV detected by PCR (>200 IU/ml) or active Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Patients whom have recently started (>14d from C1D1) antiviral therapy may go on to the trial.
- History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
- 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.
- Any evidence of current ILD or pneumonitis or a prior history of ILD or pneumonitis requiring oral or IV glucocorticoids.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Non-small-cell lung cancer (NSCLC) Dupilumab 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. Non-small-cell lung cancer (NSCLC) Cemiplimab 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.
- Primary Outcome Measures
Name Time Method Frequency of dose limiting toxicities (DLTs) up to 30 days post-treatment Safety of treatment, defined as the frequency of dose limiting toxicities (DLTs), from start of treatment up to 30 days post the administration of dupilumab.
Percentage of dose limiting toxicities (DLT) up to 30 days post-treatment Safety of treatment, defined as the percentage of dose limiting toxicities (DLTs), from start of treatment up to 30 days post the administration of dupilumab.
Major pathological response (MPR) Day of surgery, scheduled within 7 days of Day 15 Major pathological response (MPR), defined as the percentage of 90 percent or greater tumor necrosis at time of resection, as defined by expert thoracic pathologists.
- Secondary Outcome Measures
Name Time Method Event-Free Survival (EFS) 5 years Defined as the time from initial treatment of dupilumab and cemiplimab to progression of disease, recurrence of tumor following surgery, or death from any cause regardless of etiology
Number of days leading to surgery From the time of the initial dose of dupilumab to the time of surgery, average of 21 days Time to surgery defined as the time from the initial dose of dupilumab to the time of surgery, measured in days
Frequency of adverse events as measured in NCI CTCAE v5.0 up to 30 days post treatment Feasibility of treatment, defined as the frequency of treatment-related delay of curative-intent surgery, due to treatment-related Adverse Events (AEs), greater than 8 weeks following the administration of dupilumab
Overall Survival (OS) 5 years Time, in days, between treatment initiation and when the patient dies from any cause regardless of etiology
Trial Locations
- Locations (1)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States