Phase I/II Study of Neoadjuvant Cemiplimab and Dupilumab in Early-Stage Non-Small Cell Lung Cancer (Dupi-Cemi)

Phase I/II Study of Combined Treatment With Cemiplimab (Anti-PD-1) and Dupilumab (Anti-IL-4R) in Patients With Early-stage, Resectable NSCLC

This phase 1b/2a study evaluates the safety, feasibility, and efficacy of combining dupilumab (anti-IL-4Rα) and cemiplimab (anti-PD-1) in patients with early-stage, resectable NSCLC. Phase 1b focuses on safety and feasibility, using a 3+3 design to monitor dose-limiting toxicities (DLTs), while Phase 2a assesses the major pathological response (MPR) rate with a Simon's two-stage minimax design. Secondary endpoints include event-free survival, overall survival, and translational objectives such as deep immune monitoring from patient samples, with the trial expected to enroll 24 patients at CHUM over five years.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer; Neoadjuvant Therapy; Immunotherapy
• Intervention / Treatment: Drug: Cemiplimab; Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wiam Belkaid, PhD; Phone Number: 23242 514-836-3273; Email: wiam.belkaid.chum@ssss.gouv.qc.ca
• Study Contact Backup: Name: Antoine Desilets, MD, MSc; Phone Number: 514-890-8444; Email: antoine.desilets.med@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
      • Contact: Wiam Belkaid, PhD; Phone Number: 23242 514-836-3273; Email: wiam.belkaid.chum@ssss.gouv.qc.ca
      • Contact: Antoine Desilets, MD, MSc; Phone Number: 514-890-8444; Email: antoine.desilets.med@ssss.gouv.qc.ca
      • Principal Investigator: Antoine Desilets, MD, MSc
      • Sub-Investigator: Moishe Liberman, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmation of NSCLC is required before treatment (however, patients with a smoking history and radiographic findings suggestive of NSCLC may consent prior to biopsy to combine research and diagnostic procedures.
• Age ≥ 18 years.
• ECOG performance status 0-1
• Determined to be a surgical candidate for tumor resection by a multidisciplinary team.
• Women of childbearing potential and men must use approved contraception during the study and for 4 months post-treatment. Pregnancy or suspected pregnancy must be reported immediately.
• Adequate organ and marrow function.
• Pre-treatment biopsies are mandatory, and tumors must be T1b or larger (>1cm) and amenable to biopsy as determined by a multidisciplinary team.
• Patients must consent to provide blood at designated study time points.
• Patients must consent to core needle biopsies (at least 3 samples, as deemed safe by the performing surgeon/radiologist) prior to treatment initiation

Exclusion Criteria:

• History of autoimmune disorders or use of immunomodulatory drugs (including dupilumab) within 2 months prior to treatment initiation.
• Active autoimmune disease requiring systemic treatment in the past year, excluding replacement therapies like thyroxine or insulin.
• Use of immunosuppressive drugs or systemic steroids within 7 days prior to treatment, except chronic steroids ≤10mg prednisone or equivalent.
• No smoking history or confirmed tissue or ctDNA evidence of actionable driver alterations (e.g. EGFR mutation, ALK, or ROS1 rearrangements)
• Prior chemotherapy or radiotherapy for another primary tumor, or prior locoregional therapy to the target lesion. Therapy for a different cancer is acceptable.
• Metastatic disease where surgery would not have curative intent.
• Uncontrolled illness, including active infections requiring antibiotics, symptomatic heart failure, unstable angina, or psychiatric/social conditions impeding study compliance.
• Pregnancy or nursing, due to potential harm to the fetus or infant.
• Progressive malignancy requiring active treatment, except for certain stable cancers treated with curative intent
• HIV infection with detectable viral load or not on a stable HAART regimen
• Active Hepatitis B or C (PCR-detectable)
• History of allogeneic hematopoietic or solid organ transplantation.
• Documented hypersensitivity to protein therapeutics.
• Any condition, therapy, or abnormality that may interfere with trial results, patient participation, or their best interest as per the investigator's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant cemiplimab and dupilumab combination therapy; Neoadjuvant immunotherapy administered prior to thoracic surgery	Drug: Cemiplimab; Cemiplimab 350 mg administered intravenously on day 1; Drug: Dupilumab; Dupilumab 600 mg administered subcutaneously on day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	(Phase 1b) Determine the safety (dose-limiting toxicities) of combined treatment with anti-IL-4R-alpha (dupilumab) and anti-PD-1 (cemiplimab) in patients with early-stage, resectable NSCLC.	First 30 days after immunotherapy
Major pathological response (MPR) rate	(Phase 2a) Assess efficacy of combined cemiplimab and dupilumab in patients with early stage, resectable NSCLC. Efficacy is defined as percentage of patients achieving major pathological response (MPR), i.e. 90% or greater tumor necrosis at time of resection.	Day of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of curative-intent surgery	(Phase 1b and 2a) Describe and quantify rate of curative-intent surgery following treatment intervention	Day of surgery
Tolerability	(Phase 2a) Assess general tolerability in patients treated with dupilumab and cemiplimab treatment combination	For up to 5 years or until death
Event-free survival (EFS)	(Phase 1b and 2a) Assess event free survival (EFS) as it relates to neoadjuvant cemiplimab and dupilumab treatment combination and following surgery	For up to 5 years or until death
Overall survival (OS)	(Phase 1b and 2a) Assess overall survival (OS) as it relates to dupilumab and cemiplimab treatment combination and following surgery	For up to 5 years or until death
Pathological complete response (pCR) rate	(Phase 1b and 2a) Assess pathological complete response (pCR) rate	Day of surgery

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Investigators: Principal Investigator: Antoine Desilets, MD, MSc, CHUM

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Dupilumab; Neoadjuvant immunotherapy; Cemiplimab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Cemiplimab
• Other Study ID Numbers: 2025-12543

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes