A Phase 1/2 Study of Combined Treatment With Dupilumab (Anti-IL-4Ra) and Cemiplimab (Anti-PD-1) in Patients With Early-stage, Resectable NSCLC
Overview
- Phase
- Phase 1
- Intervention
- Dupilumab
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Icahn School of Medicine at Mount Sinai
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Frequency of dose limiting toxicities (DLTs)
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
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.
Investigators
Thomas Marron
Associate Professor of Medicine
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •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.
Arms & Interventions
Non-small-cell lung cancer (NSCLC)
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.
Intervention: Dupilumab
Non-small-cell lung cancer (NSCLC)
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.
Intervention: Cemiplimab
Outcomes
Primary Outcomes
Frequency of dose limiting toxicities (DLTs)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- Event-Free Survival (EFS)(5 years)
- Number of days leading to surgery(From the time of the initial dose of dupilumab to the time of surgery, average of 21 days)
- Frequency of adverse events as measured in NCI CTCAE v5.0(up to 30 days post treatment)
- Overall Survival (OS)(5 years)