Cemiplimab for Brain Metastasis from Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: EGFR, ALK, ROS1, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of cemiplimab, an immunotherapy, for non-small cell lung cancer (NSCLC) that has spread to the brain. Current treatments like radiation can cause side effects impacting the brain, so the trial aims to determine if cemiplimab can delay or reduce the need for radiation. It suits individuals with NSCLC who have at least one untreated brain metastasis and have not previously used certain immune therapies. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from cutting-edge therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on corticosteroids for brain metastases symptoms, and there are restrictions on recent chemotherapy or monoclonal antibody treatments.

Is there any evidence suggesting that cemiplimab is likely to be safe for humans?

Research has shown that cemiplimab, a treatment that aids the immune system in fighting cancer, holds promise for advanced non-small cell lung cancer (NSCLC). In previous studies, patients receiving cemiplimab achieved better outcomes than those undergoing traditional chemotherapy. Most patients tolerated the treatment well, with serious side effects being rare. Common mild side effects included tiredness and skin rash, which most patients managed effectively.

Additionally, cemiplimab has been tested in patients whose cancer had spread to the brain but wasn't causing serious symptoms. These studies suggest that cemiplimab can work effectively without introducing major new safety issues.

Cemiplimab is already FDA-approved for some cancer patients, indicating a certain level of safety. However, like any medical treatment, risks remain, and side effects can vary among individuals. It is crucial to consult healthcare professionals about potential risks when considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cemiplimab is unique because it’s an immune checkpoint inhibitor that specifically targets the PD-1 pathway. Unlike traditional treatments for brain metastasis from lung cancer, such as radiation therapy and chemotherapy, cemiplimab harnesses the power of the immune system to attack cancer cells. Researchers are excited about cemiplimab because it has the potential to offer a more targeted approach, possibly leading to better outcomes with fewer side effects. Additionally, its ability to cross the blood-brain barrier and directly impact brain metastases makes it a promising option for patients with this challenging condition.

What evidence suggests that cemiplimab might be an effective treatment for brain metastasis from lung cancer?

Research has shown that cemiplimab, a type of immunotherapy, holds promise for treating advanced non-small cell lung cancer (NSCLC), particularly in patients with high levels of the protein PD-L1. Studies have found that cemiplimab extends patients' lives and slows disease progression more effectively than traditional chemotherapy. This is especially true for patients whose cancer has spread to the brain. In these cases, cemiplimab has been more effective in controlling the disease and extending life. By boosting the immune system to attack cancer cells, cemiplimab may delay the need for radiation treatments, which can cause memory and thinking problems. Overall, it shows potential as a treatment for brain metastases in NSCLC patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Arya Amini

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer (NSCLC) that has spread to the brain, and who have high levels of a protein called PD-L1. Participants must not have used immune checkpoint inhibitors before but can have had one cycle of chemotherapy. They should be in good physical condition (ECOG <= 1), able to understand English, and willing to use birth control. People are excluded if they've had certain other treatments or conditions, including specific gene mutations or severe autoimmune diseases.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

Your liver enzyme levels are not more than 1.5 times the upper limit of normal.

I may have had one round of chemo for my current condition or had platinum-based chemo over 21 days ago.

Exclusion Criteria

I haven't had chemotherapy or targeted therapy in the last 3 weeks and have recovered from any side effects.

I cannot or do not want to have a brain MRI.

I had brain surgery more than 2 weeks ago, except for a biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab intravenously and undergo regular imaging and blood sample collection

Up to 24 months

Regular visits for IV administration and imaging

Follow-up

Participants are monitored for safety, effectiveness, and quality of life changes after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab

Trial Overview The trial is testing cemiplimab's effectiveness on untreated brain metastases from NSCLC without using upfront stereotactic radiosurgery or whole-brain radiation therapy. Cemiplimab is an immunotherapy drug designed to help the immune system fight cancer by interfering with tumor growth and spread.

How Is the Trial Designed?

Group I: Treatment (Cemiplimab) Experimental Treatment 5 Interventions

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

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a real-world study of 54 patients with advanced non-squamous non-small cell lung cancer, the combination of carboplatin, pemetrexed, and pembrolizumab showed a higher disease control rate (86.7%) compared to carboplatin and pemetrexed alone (54%).

Patients with brain metastases treated with the combination therapy had a significantly lower progression rate (33.3%) compared to those receiving only carboplatin and pemetrexed (91.7%), indicating that this regimen may be particularly effective for this challenging patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. Afzal, MZ., Dragnev, K., Shirai, K.[2023]

Targeted therapies for non-small-cell lung cancer (NSCLC) that focus on specific genetic mutations, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), have shown the ability to cross the blood-brain barrier, leading to better outcomes for patients with brain metastases.

The combination of these targeted therapies and immunotherapies, along with advanced radiation techniques, is significantly improving treatment options and prognosis for patients suffering from brain metastases associated with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer. Bulbul, A., Forde, PM., Murtuza, A., et al.[2022]

In a study of primary NSCLC adenocarcinoma tissues and cell lines, EGFR mutant cells showed better response to the targeted therapy erlotinib, while KRAS mutant and wild-type cells were more sensitive to cisplatin, indicating that treatment efficacy varies based on specific genetic mutations.

Cisplatin treatment increased the secretion of pro-inflammatory cytokines IL-6 and IL-8, which in turn enhanced cellular migration and proliferation, suggesting that the order of drug administration can influence both cytokine production and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin treatment induced interleukin 6 and 8 production alters lung adenocarcinoma cell migration in an oncogenic mutation dependent manner. Kiss, E., Abdelwahab, EHMM., Steib, A., et al.[2021]

A survey of 462 European physicians revealed that 85% routinely screen neurologically asymptomatic non-small cell lung cancer (NSCLC) patients for brain metastases (BM) at diagnosis, primarily using MRI, indicating a proactive approach to early detection.

Management of BM in NSCLC patients varies significantly across Europe, with mutation-positive (MUT+) patients receiving more intensive local treatments like stereotactic radiosurgery compared to mutation-negative (MUT-) patients, highlighting the need for standardized treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diversity of brain metastases screening and management in non-small cell lung cancer in Europe: Results of the European Organisation for Research and Treatment of Cancer Lung Cancer Group survey. Levy, A., Faivre-Finn, C., Hasan, B., et al.[2019]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

The study determined that the maximum tolerated dose (MTD) of gemcitabine when given with whole-brain radiotherapy (WBRT) for non-small cell lung cancer brain metastases is 700 mg/m², with significant toxicities observed at this level.

At a dose of 600 mg/m², gemcitabine showed no neurological toxicity, making it a safer option for further studies, despite some patients experiencing grade 4 thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer: phase I trial. Huang, YJ., Wu, YL., Xie, SX., et al.[2022]

In a study of 70 patients with non-small cell lung cancer and brain metastases, both chemotherapy regimens (triplet cisplatin-vinorelbine-ifosfamide and high-dose ifosfamide) showed similar overall response rates, particularly for brain-target lesions, but did not significantly improve overall survival outcomes.

The triplet regimen was associated with higher rates of myelotoxicity, including febrile neutropenia and infections, highlighting the need for safer treatment alternatives in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recursive Partitioning Analysis Groups II-III brain metastases of non-small cell lung cancer: a phase II randomized study comparing two concurrent chemoradiotherapy regimens. Quantin, X., Bozonnat, MC., Pujol, JL.[2010]

In a study of 150 patients with stage II/III non-small-cell lung carcinoma (NSCLC), the incidence of brain metastases (BM) was found to be significant, with a 2-year actuarial rate of 30%, particularly high in stage IIIB patients with nonsquamous tumors (42%).

The timing of chemotherapy was crucial; patients receiving chemotherapy before radiotherapy had a higher risk of developing BM (39% at 2 years) compared to those who did not delay radiotherapy (20% at 2 years), suggesting that treatment strategies may need to be adjusted to reduce BM risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced non-small-cell lung carcinoma. Robnett, TJ., Machtay, M., Stevenson, JP., et al.[2022]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

Icotinib, a new oral EGFR-TKI, was effective in treating a patient with lung adenocarcinoma and brain metastases, allowing the patient to maintain a satisfactory quality of life for one year.

This case highlights the potential of icotinib as a treatment option for patients with non-small cell lung cancer (NSCLC) who have developed brain metastases, which are common and significantly impact prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib. Zhang, Y., Tang, H., Li, J., et al.[2020]

In a study of 211 patients with advanced non-small cell lung cancer (NSCLC) and brain metastasis, the combination of immune checkpoint inhibitors (ICIs) and chemotherapy resulted in significantly higher response rates and longer progression-free survival compared to chemotherapy alone.

The ICI plus chemotherapy regimen led to an intracranial objective response rate of 44.1% and a systemic response rate of 49.0%, with median progression-free survival of 11.0 months for intracranial and 9.0 months for systemic disease, indicating its efficacy as a first-line treatment without unexpected serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer. Huang, Z., Wu, F., Xu, Q., et al.[2023]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Citations

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Cemiplimab monotherapy as first‐line treatment of patients ... Cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non–small cell lung cancer (NSCLC)

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Cemiplimab Displays Survival Benefits Over ... Cemiplimab significantly improved OS and PFS in advanced NSCLC patients with brain metastases and PD-L1 expression ≥50% compared to chemotherapy ...

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Cemiplimab for the Treatment of Untreated Brain ... 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 ...

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Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.9085

Cemiplimab monotherapy as first-line (1L) treatment of ... 1L cemiplimab monotherapy improved OS, PFS, and ORR vs chemotherapy, in patients with advanced NSCLC with PD-L1 ≥50%, and clinically stable brain metastases at ...

6. libtayohcp.com libtayohcp.com/nsclc/study-design/monotherapy

LIBTAYO® (cemiplimab-rwlc) EMPOWER-Lung 1 Phase 3 Study Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, ...

7. nature.com nature.com/articles/s41591-022-01977-y

Cemiplimab plus chemotherapy versus ... Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.