Trial Title:
Cemiplimab for the Treatment of Untreated Brain Metastases From PD-L1 >= 50% Non-Small Cell Lung Cancer
NCT ID:
NCT05840770
Condition:
Metastatic Lung Non-Small Cell Carcinoma
Metastatic Malignant Neoplasm in the Brain
Stage IV Lung Cancer AJCC v8
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Brain Neoplasms
Neoplasms
Cemiplimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (Cemiplimab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Cemiplimab
Description:
Given IV
Arm group label:
Treatment (Cemiplimab)
Other name:
Cemiplimab RWLC
Other name:
Cemiplimab-rwlc
Other name:
Libtayo
Other name:
REGN2810
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (Cemiplimab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Elastography
Description:
Undergo MRI
Arm group label:
Treatment (Cemiplimab)
Other name:
MRE
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET scan
Arm group label:
Treatment (Cemiplimab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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)
- Aspartate aminotransferase (AST) =< 1.5 x ULN (performed within 30 days prior to day
1 of protocol therapy)
- Alanine aminotransferase (ALT) =< 3 x ULN (performed within 30 days prior to day 1
of protocol therapy)
- Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault
formula (performed within 30 days prior to day 1 of protocol therapy)
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
(performed within 30 days prior to day 1 of protocol therapy)
- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
- Agreement by females and males of childbearing potential* to use an effective method
of birth control or abstain from heterosexual activity for the course of the study
through at least 6 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- No EGFR, ALK or ROS1 aberrations
- Brainstem lesion or threatening lesion adjacent to critical structures (i.e. optic
nerves/chiasm) - patients can still be enrolled if these are treated and additional
lesion(s) based on inclusion criteria above are met
- 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arya Amini
Phone:
626-218-4589
Email:
aamini@coh.org
Investigator:
Last name:
Arya Amini
Email:
Principal Investigator
Start date:
November 1, 2024
Completion date:
October 30, 2029
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05840770
