This phase II trial tests how well cemiplimab works in treating patients with PD-L1 \>= 50% non-small cell lung cancer (NSCLC) that has spread from where it first started (primary site) to the brain (metastases). Approximately 10% of patients diagnosed with metastatic NSCLC present with brain metastases and another 30% develop brain metastases during the illness. Currently, the management of brain metastases relies on stereotactic radiosurgery (SRS), which has high rates of local control, but in combination with systemic therapy, can cause certain toxicities, including central nervous system (CNS) necrosis or potential cognitive changes or memory deficits. Additionally, in patients with numerous brain metastases, whole brain radiation (WBRT) is recommended, leading to significant neurocognitive deficits. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. However, there is little data on the effectiveness of newer systemic therapies, such as immunotherapy, in penetrating and treating previously untreated brain metastases. Cemiplimab without upfront SRS or WBRT for asymptomatic brain metastases may help delay the need for radiation in patients with untreated brain metastases from PD-L1 \>= 50% NSCLC.
PRIMARY OBJECTIVE: I. To evaluate if CNS control rate defined as complete response (CR), partial response (PR), or stable disease (SD), is acceptable with a strategy of cemiplimab alone for patients with advanced NSCLC, PD-L1 \>= 50%, no EGFR, ALK or ROS1 aberrations with untreated brain metastases. SECONDARY OBJECTIVES: I. To evaluate time until intracranial progression with cemiplimab alone. II. To evaluate time to extracranial progression . III. To evaluate overall survival (OS). IV. To evaluate CNS objective response rate (ORR) defined as CR and PR. V. To evaluate time until administration of radiation therapy (RT), either SRS or WBRT. VI. To report longitudinal changes in quality of life with cemiplimab alone. EXPLORATORY OBJECTIVES: I. To bank blood and tissue specimens for predictive biomarker analyses evaluating CNS disease control and survival outcomes in patients treated with cemiplimab. OUTLINE: Patients receive cemiplimab intravenously (IV) and undergo blood sample collection while on study. Patients undergo magnetic resonance imaging (MRI), computed tomography (CT) scan and position emission tomography (PET) scan throughout the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Undergo blood sample collection
Given IV
Undergo CT scan
Undergo MRI
Undergo PET scan
Central nervous system (CNS) control rate
Includes complete response (CR), partial response (PR), and stable disease (SD) using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Time frame: At 4 weeks
Time until any CNS progression
Measured by RANO-BM criteria .
Time frame: Up to 12 months from time of enrollment
Extracranial progression free survival
Defined as first occurrence of disease progression by Positron Emission Response Criteria in Solid Tumors version (v) 1.0 or Response Evaluation Criteria in Solid Tumors v1.1.
Time frame: From enrollment to progression or death due to any cause, assessed up to 2 years
Time until administration of whole brain radiation therapy or stereotactic radiosurgery
Time frame: Up to 5 years
Incidence of adverse events
Rate of all grades and grade \>= 3 toxicities at least possibly related to study therapy as measured by Common Terminology Criteria for Adverse Events v 5.0.
Time frame: Up to 2 years
Overall survival
Time frame: From the date of study enrollment to the date of death from any cause, assessed up to 5 years
Time until brain metastases-specific mortality
Defined as intracranial progression as a component of cause of death per RANO-BM criteria.
Time frame: Up to 24 months from enrollment
Cumulative rate of best responses
Individually for CR, PR, SD as defined by the RANO-BM criteria.
Time frame: Up to 5 years
Longitudinal changes in patient-reported quality of life - Measurement I
Measured by using the MD Anderson Symptom Inventory-Brain Tumor, Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form (4a), and linear analogue self-assessment single-item numerical scale.MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT): scale of 0 (not present) - 10 (as bad as you can imagine). 28 questionnaire with minimum score of 0 (best score) and maximum score of 280 (worse score).
Time frame: Baseline to day 42
Longitudinal changes in patient-reported quality of life - Measurement II
Measured by using Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function Short Form. Scale of 5 (never) - 1 (very often/several times a day). 6 questions with a minimum score of 6 (worse score) and maximum score of 30 (best score).
Time frame: Baseline to day 42
Longitudinal changes in patient-reported quality of life - Measurement III
Measured by using Linear Analogue Self-Assessment (LASA) Single-Item Numerical Scale. Scale of 0 (as bad as it can be) - 10 (as good as it can be). 5 questions with a minimum score of 0 (worse score) and maximum score of 50 (best score).
Time frame: Baseline to day 42
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