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

NCT ID: NCT06743581

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2030-02-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant cemiplimab and dupilumab combination therapy

Neoadjuvant immunotherapy administered prior to thoracic surgery

Group Type: EXPERIMENTAL

Cemiplimab

Intervention Type: DRUG

Cemiplimab 350 mg administered intravenously on day 1

Dupilumab

Intervention Type: DRUG

Dupilumab 600 mg administered subcutaneously on day 1

Interventions

Cemiplimab

Cemiplimab 350 mg administered intravenously on day 1

Intervention Type: DRUG

Dupilumab

Dupilumab 600 mg administered subcutaneously on day 1

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoine Desilets, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

CHUM

Locations

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Countries

Canada

Central Contacts

Antoine Desilets, MD, MSc

Role: CONTACT

Phone: 514-890-8444

Email: antoine.desilets.med@ssss.gouv.qc.ca

Wiam Belkaid, PhD

Role: CONTACT

Phone: 514-836-3273

Email: wiam.belkaid.chum@ssss.gouv.qc.ca

Facility Contacts

Antoine Desilets, MD, MSc

Role: primary

Wiam Belkaid, PhD

Role: backup

References

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.

Reference Type: RESULT

PMID: 38057662 (View on PubMed)

Other Identifiers

2025-12543

Identifier Type: -

Identifier Source: org_study_id