Using cemiplimab and fianlimab before surgery for non-small cell lung cancer

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 study is testing a combination of two drugs, cemiplimab and fianlimab, before surgery to see if they can help people with stage IB-IIIB non-small cell lung cancer respond better to treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: radiation, prednisone, cemiplimab, fianlimab, chemotherapy, immunotherapy
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT06918132 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of a fixed dose combination of cemiplimab and fianlimab as neoadjuvant therapy for patients with stage IB-IIIB non-small cell lung cancer (NSCLC). The study aims to determine the rate of major pathologic response (MPR) in patients with varying levels of PD-L1 expression. Secondary objectives include assessing event-free survival, overall survival, and disease-free survival, along with the analysis of biomarkers and tumor characteristics. The trial involves biospecimen collection and imaging to monitor treatment effects and surgical feasibility.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed stage IB-IIIB NSCLC and measurable disease.

Not a fit: Patients with tumors that are not resectable or those with PD-L1 expression below 1% may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve tumor response rates and surgical outcomes for patients with early-stage non-small cell lung cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in treating non-small cell lung cancer, indicating potential for success in this trial.

Eligibility criteria

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

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Kaushal Parikh, MBBS — Mayo Clinic
• Study coordinator: Clinical Trials Referral Office

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