Trial Title:
Neoadjuvant Dupilumab and Cemiplimab in Patients With Early-stage Resectable NSCLC
NCT ID:
NCT06088771
Condition:
Non-Small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Cemiplimab
Conditions: Keywords:
Neoadjuvant
Dupilumab
Cemiplimab
Resectable
anti-PD1
Anti-IL-4Ra
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Phase 1b of the study will consist of a safety run-in phase following a modified 3+3
design without dose escalation using the treatment administration plan in protocol
patients will be enrolled and monitored for dose-limiting toxicities (DLTs), from the
start of treatment up to 30 days following the administration of dupilumab. Patients will
be entered in escalating cohorts of 3 patients.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Dupilumab
Description:
Dupilumab will be administered at the recommended initial dosage of 600 mg (two 300 mg
injections) on Day 1.
Arm group label:
Non-small-cell lung cancer (NSCLC)
Other name:
Dupixent
Intervention type:
Biological
Intervention name:
Cemiplimab
Description:
Cemiplimab will be administered at the recommended dosage of 350 mg, as an intravenous
infusion, over 30 minutes on Day 1.
Arm group label:
Non-small-cell lung cancer (NSCLC)
Other name:
Libtayo
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- Histological diagnosis of NSCLC is required before initiation of treatment, however,
patients who have a smoking history and radiographic findings highly suggestive of a
diagnosis of NSCLC who are scheduled to undergo diagnostic biopsy may be consented
so as they can undergo the biopsy mandated for research at the same time to avoid
second procedure. Pre-treatment biopsies are mandatory before treatment initiation.
Patients with NSCLC must have T1b or more advanced (>1cm primary tumor). Only
patients whose tumor is deemed amenable to surgical or needle biopsy by a
multidisciplinary team including a medical oncologist and an interventionalist
(radiologist, surgeon, pulmonologist) may be enrolled.
- Patient must be willing and able to provide blood samples (6 heparinized tubes, 2
streck tubes, roughly 60mL) at the time points indicated in the Study Calendar.
- Patient must be willing and able to have core needle biopsies (Goal 3-6 biopsies,
final number to be determined by the surgeon and radiologist performing the
procedure as safe) of tumor prior to initiation of therapy.
- Age ≥ 18 years.
- ECOG 0-1. 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.
- Patient is determined to be a surgical candidate for resection of their tumor by a
multidisciplinary team including a surgeon and a medical oncologist.
- Women of child-bearing potential and men must agree to use adequate contraception
upon 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 (i.e., has
had menses at any time in the preceding 12 consecutive months).
- Ability to understand and the willingness to sign a written informed consent.
- Adequate organ and marrow function as defined below:
- System/Laboratory Value
- Hematologic:
Absolute neutrophil count (ANC) ≥1,000 /mcL Platelets ≥75,000 /mcL Hemoglobin ≥9 g/dL
- Renal* Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60
mL/min for patient with creatinine levels > 1.5 X institutional ULN Creatinine
clearance should be calculated per institutional standard.
- Hepatic* Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients
with total bilirubin levels > 1.5 ULN AST and ALT ≤ 2.5 X ULN Albumin >2.5 mg/dL
- Coagulation* International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X
ULN unless patient is receiving anticoagulant therapy as long as PT is within
therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless patient is receiving
anticoagulant therapy as long as PTT is within therapeutic range of intended use of
anticoagulants
- If laboratory criteria are not met due to what the investigator determines to
be a biologic cause (e.g. Gilbert's syndrome causing elevated bilirubin or
excessive muscle mass affecting creatinine) or drug-related cause (e.g.
elevating in transaminases due to HAART therapy, elevated INR due to
anticoagulation) then the lab values will not be used to exclude patient from
this trial. Similarly, for patients with elevated bilirubin due to biliary
obstruction from tumor, this will not serve as an exclusion criterion. This
determination will be made by the PI.
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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Thomas Marron, MD PhD
Phone:
212-824-9472
Email:
thomas.marron@mssm.edu
Contact backup:
Last name:
Katherine Vandris
Email:
Katherine.Vandris@mssm.edu
Investigator:
Last name:
Thomas Marron, MD
Email:
Principal Investigator
Start date:
March 8, 2024
Completion date:
March 2032
Lead sponsor:
Agency:
Icahn School of Medicine at Mount Sinai
Agency class:
Other
Source:
Icahn School of Medicine at Mount Sinai
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06088771
