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

NCT06743581 | Not Yet Recruiting DMC

• 1 other identifier: 2025-12543
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer; Immunotherapy; Neoadjuvant Therapy

Keywords

NSCLC; Neoadjuvant immunotherapy; Cemiplimab; Dupilumab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Rate of curative-intent surgery

  Day of surgery

• Tolerability

  For up to 5 years or until death

• Event-free survival (EFS)

  For up to 5 years or until death

• Overall survival (OS)

  For up to 5 years or until death

• Pathological complete response (pCR) rate

  Day of surgery

Study Arms (1)

Neoadjuvant cemiplimab and dupilumab combination therapy

EXPERIMENTAL

Neoadjuvant immunotherapy administered prior to thoracic surgery

Drug: Cemiplimab; Drug: Dupilumab

Interventions

Cemiplimab DRUG

Cemiplimab 350 mg administered intravenously on day 1

Neoadjuvant cemiplimab and dupilumab combination therapy

Dupilumab DRUG

Dupilumab 600 mg administered subcutaneously on day 1

Neoadjuvant cemiplimab and dupilumab combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

Related Publications (1)

• 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.

  PMID: 38057662 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab; dupilumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Antoine Desilets, MD, MSc

  CHUM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antoine Desilets, MD, MSc

CONTACT

514-890-8444; antoine.desilets.med@ssss.gouv.qc.ca

Wiam Belkaid, PhD

CONTACT

514-836-3273; wiam.belkaid.chum@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

CA (1)