phase i/ii study of neoadjuvant cemiplimab and dupilumab in early-stage non-small cell lung cancer

Conditions: Non-Small Cell Lung Cancer; Immunotherapy; Neoadjuvant Therapy

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.

Keywords: nsclc neoadjuvant immunotherapy cemiplimab dupilumab