Cemiplimab and Fianlimab Before Surgery for the Treatment of Stage IB-IIIB Non-Small Cell Lung Cancer (N-PLANC)

Phase II Single Arm Study of Neoadjuvant Dual Checkpoint Blockade With Programmed Death-ligand 1 (PD1) and Lymphocyte Activation Gene 3 (LAG-3) Inhibition in Resectable Non-Small Cell Lung Cancer (N-PLANC)

This phase II trial tests how well a fixed dose combination (FDC) of cemiplimab and fianlimab before surgery (neoadjuvant) works in treating patients with stage IB-IIIB non-small cell lung cancer (NSCLC). The current standard of care (SOC) for NSCLC is to give chemotherapy and immunotherapy before going to surgery to have the cancer removed (neoadjuvant therapy). Immunotherapy with monoclonal antibodies, such as cemiplimab and fianlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a FDC of cemiplimab and fianlimab before surgery may kill more tumor cells in treating patients with stage IB-IIIB NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Lung Non-Small Cell Carcinoma; Stage II Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Biological: Cemiplimab; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Surgical Procedure; Procedure: Biospecimen Collection; Biological: Fianlimab

Detailed Description

PRIMARY OBJECTIVES:

I. To assess efficacy of neoadjuvant cemiplimab and fianlimab in patients with resectable/early-stage NSCLC with programmed death-ligand 1 (PD-L1) 1-49%, as measured by rate of major pathologic response (MPR) (defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes).

II. To assess efficacy of neoadjuvant cemiplimab and fianlimab in patients with resectable/early-stage NSCLC with PD-L1 ≥ 50%, as measured by rate of major pathologic response (MPR).

SECONDARY OBJECTIVES:

I. Assess the following endpoints (overall and by PD-L1 subsets): event-free survival (EFS), overall survival (OS), disease-free survival (DFS), response rate, pathological complete response rate (pCR), surgical feasibility, and adverse events.

OTHER GOALS (done overall and by PD-L1 subsets):

I. Assess the following in an exploratory fashion: residual viable tumor cells using various cutpoints, whole exome sequencing (WES), gene copy number analysis, circulating tumor deoxyribonucleic acid (DNA) (ctDNA) analysis, tumor microenvironment (TME) analysis, microbiome analyses, temporal biomarker changes.

II. Assess LAG-3 expression on immune-cells by immunohistochemistry (IHC) (17B4) and major histocompatibility complex class II (MHC-II) and fibrinogen-like protein 1 (FGL1) expression by on tumor cells and correlate with clinical data like MPR rate, EFS, and OS.

III. Determine any correlation between the above biomarkers with clinical data of interest like the MPR rate, EFS, and OS.

IV. Determine ctDNA testing as a marker for minimal residual disease (MRD) and molecular recurrence.

OUTLINE:

Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle and fianlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) during screening, tissue sample collection on study and blood sample collection on study and follow-up. Patients may undergo SOC surgery post-treatment.

After completion of study treatment, patients are followed up at 90 days, then every 3 months post-surgery for the first 2 years, then every 6 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Kaushal Parikh, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years

• Disease characteristics:

  • Histologically or cytologically confirmed stage IB-IIIB (N2) non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Cancer Staging Manual Eighth Edition
  • T4 tumors will only be eligible if they are defined as T4 based only on their size (more than 7 cm). All other T4 tumors will be ineligible.
  • Pathologic status of lymph nodes must be known for suspicious or enlarged lymph nodes. Note: suspicious or enlarged lymph nodes must be discussed with sponsor/principal investigator.

  • PD-L1 expression ≥ 1% by tumor proportion score (TPS) using immunohistochemistry (IHC)

    • Group A: PD-L1 expression ≥ 1% < 50%
    • Group B: PD-L1 expression ≥ 50%
  • Complete surgical resection of the primary NSCLC must be deemed achievable by thoracic surgeon at screening
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Adequate pulmonary function ascertained by treating surgeon obtained ≤ 30 days prior to registration. A pre- or post-bronchodilator forced expiratory volume in 1 second (FEV1) of 1.0 L or > 40% postoperative predicted value or diffusing capacity of the lungs for carbon monoxide (DLCO) > 40% predicted value are required prior to enrollment
• Hemoglobin ≥ 8.0 g/dL (obtained ≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm^3 (obtained ≤ 15 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (obtained ≤ 15 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained ≤ 15 days prior to registration)
• Calculated creatinine clearance ≥ 45 ml/min using the Cockroft-Gault formula (obtained ≤ 15 days prior to registration)
• Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Willingness to provide mandatory blood specimens for correlative research
• Willingness to provide mandatory tissue specimens for correlative research
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential or able to father a child who are unwilling to employ highly effective contraception during the study and up to 6 months after the last dose
• Presence of targetable alterations [Epiderman Growth Factor Receptor (EGFR), anaplastic lymphoma kinase (ALK), receptor tyrosine kinase (ROS1)] in tumor
• Unresectable or metastatic disease

• Active or history of the following:

  • Prior systemic anti-cancer therapy or radiation therapy for the same cancer being studied in this protocol
  • Interstitial lung disease (e.g., idiopathic pulmonary fibrosis or organizing pneumonia), or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or pneumonitis within the last 5 years
  • Autoimmune disease (including any history of inflammatory bowel disease)
  • Any syndrome that required systemic steroids or immunosuppressive medications EXCEPTIONS: patients with vitiligo; resolved childhood asthma/atopy; residual hypothyroidism that requires only hormone replacement; or psoriasis not requiring systemic treatment, type-1 diabetes mellitus, or rheumatoid arthritis managed without disease modifying anti-rheumatic drugs or >10 mg prednisone equivalent
• Patients requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications ≤14 days prior to registration.

NOTE: Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

• Patients with organ transplantation
• History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias; or prior immune-related myocarditis

• Uncontrolled intercurrent non-cardiac illness including, but not limited to:

  • Ongoing or active infection
  • Psychiatric illness/social situations
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  • Any other conditions that would limit compliance with study requirements
• Uncontrolled infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) or diagnosis of immunodeficiency that is related to, or results in chronic infection.

Note: No testing is required for this study unless mandated by local health authority.

EXCEPTIONS:

• Patients with known HIV who have controlled infection [undetectable viral load and cluster of differentiation 4 (CD4) count above 350 either spontaneously or on a stable antiviral regimen] are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.
• Patients with known hepatitis B (hepatitis B surface antigen positive [HBsAg+]) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
• Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV ribonucleic acid (RNA) by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

• Patients with HIV or hepatitis must be reviewed by a qualified specialist (e.g., infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

  • Receiving any other investigational agent which would be considered as a treatment for the primary malignancy
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Patients with a prior or concurrent malignancy whose natural history or treatment does have the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Known hypersensitivity to the active substances or to any of the excipients
  • Receipt of live vaccine ≤ 30 days prior to registration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (cemiplimab, fianlimab); Patients receive cemiplimab IV over 30 minutes on day 1 of each cycle and fianlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI during screening, tissue sample collection on study, and blood sample collection, CT, and PET/CT throughout the study. Patients may undergo SOC surgery post-treatment.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; REGN 2810; REGN-2810; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: PET; Medical Imaging; positron emission tomography scan; Pet Scan; Procedure: Computed Tomography; Undergo CT and PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; Computerized Tomography (CT) scan; Diagnostic CAT Scan; computerized axial tomogrpahy; Ct Scan; Procedure: Surgical Procedure; Undergo SOC surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, Not Otherwise Specified (NOS); Procedure: Biospecimen Collection; Undergo tissue and blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Biological: Fianlimab; Given IV; Other Names: REGN3767; Anti-LAG-3 MoAb REGN3767; REGN 3767; WHO 11182

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR) rate (Group A)	Will be defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes. Will be conducted using two parallel Simon two-stage trial designs. Will be evaluated within the PD-L1 1-49% group.	Up to 2 years
MPR rate (Group B)	Will be defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes. Will be conducted using two parallel Simon two-stage trial designs. Will be evaluated within the PD-L1 ≥ 50% group.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Defined as the time from study entry to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause (whichever occurs first).	Up to 5 years
Overall survival (OS)	Defined as the time from study entry to death from any cause.	Up to 5 years
Disease-free survival (DFS)	Defined as the time from surgery to the first of either disease recurrence or death from any cause.	Up to 5 years
Overall response rate (ORR)	Will be calculated based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A tumor response is defined to be either a complete response or partial response noted as the objective status during neoadjuvant treatment.	Up to 5 years
Pathologic complete response (pCR) rate	Defined as 0% residual viable tumor (complete absence of tumor) in the resected lung and lymph node tissue. Will be reported as pCR rate, defined as the proportion of patients who achieve pCR after neoadjuvant treatment at the time of resection	Up to 5 years
Surgical feasibility - to surgery	Will be assessed by the number of participants who make it to surgery	Up to 5 years
Surgical feasibility - complete surgery	Will be assessed by the number of participants who complete surgery	Up to 5 years
Incidence of adverse events	The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Frequency and percentage of Grade 3+ adverse events will be summarized.	Up to 90 days after last study treatment, up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Kaushal Parikh, MBBS, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2027

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Physical Phenomena; Chemistry Techniques, Analytical; Spectrum Analysis; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Specimen Handling; Magnetic Resonance Spectroscopy; Surgical Procedures, Operative; X-Rays; cemiplimab
• Other Study ID Numbers: MC230202 (Other Identifier: Mayo Clinic); NCI-2025-02153 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 23-011212 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No