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

Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
United States
New York
Icahn School of Medicine at Mount Sinai
RECRUITING
New York
Contact Information
Primary
Thomas Marron, MD, PhD
thomas.marron@mssm.edu
(212) 824-9472
Backup
Katherine Vandris
Katherine.Vandris@mssm.edu
Time Frame
Start Date: 2024-03-08
Estimated Completion Date: 2027-04-22
Participants
Target number of participants: 21
Treatments
Experimental: 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.
Sponsors
Leads: Icahn School of Medicine at Mount Sinai

This content was sourced from clinicaltrials.gov