Study of Neoadjuvant Cemiplimab and Dupilumab in Early-Stage Non-Small Cell Lung Cancer

ConditionsNon-Small Cell Lung Cancer Immunotherapy Neoadjuvant Therapy

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorCentre hospitalier de l'Université de Montréal (CHUM)

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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)

Trial design

Design model

Single group

Treatments tested in this trial

Cemiplimab
Drug
Cemiplimab 350 mg administered intravenously on day 1
Dupilumab
Drug
Dupilumab 600 mg administered subcutaneously on day 1

Treatment groups

24 Participants

are divided into 1 treatment group

Group A: Neoadjuvant cemiplimab and dupilumab combination therapyExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Safety

(Phase 1b) 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.

Time frame

First 30 days after immunotherapy

Efficacy

(Phase 2a) 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.

Time frame

Day of surgery

Secondary outcomes

Rate of curative-intent surgery

(Phase 1b and 2a) Rate of curative-intent surgery following treatment intervention

Time frame

Day of surgery

Safety and Tolerability

(Phase 2a) Safety and tolerability in patients treated with dupilumab and cemiplimab treatment combination

Time frame

For up to 5 years or until death

Event-free survival (EFS)

(Phase 1b and 2a) Event free survival (EFS) as it relates to neoadjuvant cemiplimab and dupilumab treatment combination and following surgery

Time frame

For up to 5 years or until death

Overall survival (OS)

(Phase 1b and 2a) Overall survival (OS) as it relates to dupilumab and cemiplimab treatment combination and following surgery

Time frame

For up to 5 years or until death

Other outcomes

Detection of recurrence ahead of radiographic evidence of recurrence

The creation of dynamic atlases documenting the evolution of a patient's TME, comparing pre-treatment biopsy and blood with subsequent tumor resection and blood collection. The formation of this atlas involves histologic, immunologic, genetic and radiomic characterization of the tumor both in bulk and at the single cell level, across time (from pre-treatment biopsy to biopsy upon recurrence) and across patients, and potentially even organ specific cohorts. ctDNA will be measured at multiple time points during treatment using an investigational available assay, and the ability of this assay to detect recurrence ahead of radiographic evidence of recurrence measured.

Time frame

Day 1, Day 4, Day 8, Day 15, Day of surgery and Day 30 and at recurrence if applicable

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Centre hospitalier de l'Université de Montréal (CHUM)

Lead sponsor

Source ClinicalTrials.gov

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