Clinical trial NCT06743581: Phase I/II Study of Neoadjuvant Cemiplimab and Dupilumab in Early-Stage Non-Small Cell Lung Cancer
Official title: Phase I/II Study of Combined Treatment With Cemiplimab (Anti-PD-1) and Dupilumab (Anti-IL-4R) in Patients With Early-stage, Resectable NSCLC
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Non-Small Cell Lung Cancer
Immunotherapy
Neoadjuvant Therapy
Keywords: NSCLC
Neoadjuvant immunotherapy
Cemiplimab
Dupilumab
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
First posted: 2024-12-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety
timeFrame: First 30 days after immunotherapy
measure: Major pathological response (MPR) rate
timeFrame: Day of surgery
Secondary outcomes:
measure: Rate of curative-intent surgery
timeFrame: Day of surgery
measure: Tolerability
timeFrame: For up to 5 years or until death
measure: Event-free survival (EFS)
timeFrame: For up to 5 years or until death
measure: Overall survival (OS)
timeFrame: For up to 5 years or until death
measure: Pathological complete response (pCR) rate
timeFrame: Day of surgery
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
Study officials:
affiliation: CHUM
name: Antoine Desilets, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.