Cemiplimab for the Treatment of Untreated Brain Metastases From PD-L1 >= 50% Non-Small Cell Lung Cancer

NCT05840770 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 22346NCI-2023-02193P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Neoplasm in the Brain; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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.

  At 4 weeks

Secondary Outcomes (10)

• Time until any CNS progression

  Up to 12 months from time of enrollment

• Extracranial progression free survival

  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

  Up to 5 years

• Incidence of adverse events

  Up to 2 years

• Overall survival

  From the date of study enrollment to the date of death from any cause, assessed up to 5 years

Study Arms (1)

Treatment (Cemiplimab)

EXPERIMENTAL

Patients receive cemiplimab IV and undergo blood sample collection while on study. Patients undergo MRI, CT scan and PET scan throughout the study.

Procedure: Biospecimen Collection; Biological: Cemiplimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Elastography; Procedure: Positron Emission Tomography

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Cemiplimab)

Cemiplimab BIOLOGICAL

Given IV

Also known as: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810

Treatment (Cemiplimab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (Cemiplimab)

Magnetic Resonance Elastography PROCEDURE

Undergo MRI

Also known as: MRE

Treatment (Cemiplimab)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (Cemiplimab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 1
• Ability to read and understand English for questionnaires
• Histologically confirmed non-small cell lung cancer (NSCLC)
• PD-L1 \>= 50%
• Advanced disease
• Measurable disease in the brain \>= 1 untreated brain metastasis (measuring 5-15 mm) on brain MRI with contrast within 30 days of enrollment
• Patients must not require corticosteroids for the management of symptoms from their brain metastases in the opinion of the treating investigator
• Patients must be naïve to immune check point inhibitors targeting PD-1 and PD-L1
• Prior treatment with chemotherapy is allowed. Patients who have started chemotherapy for their current disease presentation may have received up to 1 cycle of chemotherapy alone (without cemiplimab) prior to enrollment and the initiation of the protocol-specified regimen of cemiplimab. In patients who have previously received platinum-based chemotherapy for a prior disease presentation, for eligibility there must be at least 21 days since the last exposure to platinum-based chemotherapy
• Prior exposure to immune checkpoint inhibitors targeting PD-1 and/or PD-L1 is allowed if patients have been off of therapy for at least 1 year Life expectancy \>= 3 months in the opinion of the treating investigators
• Up to 10 asymptomatic (defined as no neurologic symptoms at presentation and not requiring steroids) brain lesions allowed up to 15 mm in size. Patients with lesions \> 15 mm or with a lesion at or near a critical structure (i.e. brainstem, optic structures) may still be eligible if that lesion(s) is treated and others are available that fit the above criteria
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol therapy)

You may not qualify if:

• No EGFR, ALK or ROS1 aberrations
• Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months; patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study; subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study; subjects with hypothyroidism stable on hormone replacement are not excluded from this study
• Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, whichever is shorter, prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy or targeted small molecule therapy within 3 weeks prior to administration of the study drug or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent;
• Note: Subjects with permanent =\< grade 2 toxicities (e.g. neuropathy) or toxicities corrected through routine medical management (e.g. thyroid replacement for hypothyroidism), are an exception to this criterion and may qualify for the study;
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy; \*Note: Subjects with =\< grade 2 amylase or lipase elevations abnormalities that have no corresponding clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy or any additional tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy) for at least 2 years prior to enrollment
• Prior whole brain radiation
• Has known carcinomatous meningitis (also known as leptomeningeal disease)
• Is taking \> 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required \> 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment
• \> 10 brain metastases
• Patients whose tumor exhibit activating EGFR mutation, ALK or ROS translocation and have a standard of care molecular targeted therapy available for these mutations, will be excluded from this study; adenocarcinoma patients may be consented prior to the EGFR and ALK status being known, but EGFR and ALK status must be determined prior to initiating therapy
• Previous CNS surgery within 2 weeks of treatment, with the exception of biopsy
• Unable or unwilling to undergo an intracranial MRI
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Lung Neoplasms

Interventions

Specimen Handling; cemiplimab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Arya Amini

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: May 3, 2023
• Study Start: April 15, 2025
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): October 30, 2029
• Last Updated: May 26, 2025

Record last verified: 2025-05