Recruiting
Phase 2

Cemiplimab & Fianlimab

Sponsor:

Mayo Clinic

Code:

NCT06918132

Conditions

Lung Non-Small Cell Carcinoma

Stage IB Lung Cancer AJCC v8

Stage II Lung Cancer AJCC v8

Stage IIIA Lung Cancer AJCC v8

Stage IIIB Lung Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Cemiplimab

Fianlimab

Magnetic Resonance Imaging

Surgical Procedure

Study Details

Brief summary:

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.

Conditions

Lung Non-Small Cell Carcinoma

Stage IB Lung Cancer AJCC v8

Stage II Lung Cancer AJCC v8

Stage IIIA Lung Cancer AJCC v8

Stage IIIB Lung Cancer AJCC v8

Study ID

NCT06918132

Start date

May 2, 2025

Status verified date

Sep, 2026

Completion date

Dec 2, 2033

Anticipated

Primary completion date

Dec 2, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

60 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Biospecimen Collection

Undergo tissue and blood sample collection

Cemiplimab

Given IV

Fianlimab

Given IV

Magnetic Resonance Imaging

Undergo MRI

Surgical Procedure

Undergo SOC surgery

Computed Tomography

Undergo CT and PET/CT

Positron Emission Tomography

Undergo PET/CT

Primary outcome measure

  • Major pathologic response (MPR) rate (Group A) [ Time Frame: Up to 2 years ]
  • MPR rate (Group B) [ Time Frame: Up to 2 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Principal Investigator:

Kaushal Parikh, MBBS

More Information

Sponsor

Mayo Clinic

Last update posted

Oct 1, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-10-01. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.