Perioperative Cemiplimab for Resectable Non-Small Cell Lung Cancer With High PD-L1

NCT07450183 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: HFH-C-2025-06
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II trial enrolling patients with stage II-IIIA non-small cell lung cancer whose disease is deemed amenable for surgical resection and has a PD-L1 level of ≥50%. Patients will receive cemiplimab for 3 cycles followed by surgical resection. The primary endpoint evaluated by the study is the amount of residual tumor in the resected tissue after 3 cycles of cemiplimab. After surgery, all patients will receive additional 10 cycles of cemiplimab and the treating oncologist will decide on the need of administering chemotherapy prior to that.

Conditions

Lung Cancer (NSCLC)

Keywords

Cemiplimab; Stage II lung cancer; Stage IIIA lung cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate

  At surgical resection visit

Secondary Outcomes (6)

• Event-Free Survival

  From treatment initiation until event or end of follow-up.

• Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0

  From first dose through end of treatment and safety follow-up

• Correlation of MRD Status With pCR, EFS, and OS

  Baseline, surgical resection visit, and at 6,9, and 12 months after surgery

• MRD Status by MRD Assay

  Baseline, post-resection, and at 6, 9, and 12 months after surgery.

• Major Pathological Response Rate

  At surgical resection visit

Study Arms (1)

Perioperative Cemiplimab

EXPERIMENTAL

Patients receive neoadjuvant cemiplimab 350 mg IV every 3 weeks for 3 cycles, followed by surgical resection, then adjuvant cemiplimab 350 mg IV every 3 weeks for 10 cycles. Treating oncologists may administer histology-matched adjuvant chemotherapy (up to 4 cycles) before adjuvant cemiplimab per investigator discretion.

Drug: Cemiplimab; Drug: Adjuvant chemotherapy

Interventions

Cemiplimab DRUG

Cemiplimab 350 mg IV every 3 weeks for 3 neoadjuvant cycles, followed by surgical resection, then 10 adjuvant cycles of cemiplimab at the same dose and schedule.

Perioperative Cemiplimab

Adjuvant chemotherapy DRUG

Up to 4 cycles of histology-matched platinum-based adjuvant chemotherapy may be administered after surgery, at the treating oncologist's discretion, prior to starting adjuvant cemiplimab.

Perioperative Cemiplimab

Eligibility Criteria

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

You may qualify if:

• Participant is willing and able to give informed consent for participation in the trial
• Male or Female, aged 18 years or above
• ECOG 0-1
• Patient diagnosed with early-stage resectable stage II to IIIA squamous or non-squamous, operable treatment naïve NSCLC with PD-L1 TPS ≥50%. Patients who are eligible for standard of care treatment are allowed as well as those who are ineligible for chemo, if they fit the rest of the criteria
• PD-L1 TPS ≥50% as assessed by DAKO 22C3 assay
• Adequate bone marrow function, as determined by hematological parameters:
• ANC ≥1.5 x 10\^9/L (1500/mm3)
• Hemoglobin ≥9.0 g/dL (5.59 mmol/L).
• Platelet count ≥75,000/mm³
• Adequate hepatic function, as determined by:
• AST/ALT for adults: AST ≤3x ULN, ALT ≤3x ULN
• Serum bilirubin ≤1.5x ULN, except in patients with clinically documented Gilbert's Syndrome where ≤3x the ULN is permitted
• Adequate kidney function as determined by serum creatinine ≤1.5x ULN OR calculated CrCl ≥50 ml/min (using the Cockcroft-Gault formula)
• Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use highly effective contraception during the trial and for 4 months thereafter\*.
• Participant has clinically acceptable laboratory and ECG results (specify any other additional assessments) during screening.

You may not qualify if:

• Patients showing evidence of any distant metastases during screening.
• Patients with tumors with known actionable EGFR gene mutations, ALK, RET or ROS1 gene translocations
• Any condition that requires ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
• Significant renal or hepatic impairment.
• Presence of cardiovascular disease, as defined by:
• a. New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication; or b. Transient ischemic attack or stroke within 1 year
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Participant with life expectancy of less than 6 months or is inappropriate for placebo medication.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments within the last 2 years.
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
• Uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
• Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
• Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.
• Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.

Sponsors & Collaborators

• Henry Ford Health System: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Henry Ford Health

Detroit, Michigan, 48202, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 16, 2026
• First Posted: March 4, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)