What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors and chemotherapy. Immune checkpoint inhibitors, such as Cemiplimab (an anti-PD-1 monoclonal antibody) and investigational drugs like Fianlimab (an anti-LAG-3 monoclonal antibody), work by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. Chemotherapy involves cytotoxic agents like paclitaxel and carboplatin, which kill rapidly dividing cancer cells by interfering with their DNA replication. These treatments are crucial for NSCLC patients as they can improve survival rates and quality of life by targeting cancer cells through different mechanisms, potentially leading to more effective and comprehensive cancer control.

What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors such as cemiplimab (an anti-PD-1 monoclonal antibody) include rash, colitis, pneumonitis, and other immune-related toxicities. Chemotherapy agents, such as paclitaxel, carboplatin, pemetrexed, and cisplatin, often cause side effects like nausea, vomiting, hair loss, fatigue, and increased risk of infection due to lowered blood cell counts. Combining these treatments can lead to a range of side effects, including those from both immunotherapy and chemotherapy, necessitating careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several treatments for NSCLC that involve immune checkpoint inhibitors combined with chemotherapy. Notably, pembrolizumab (an anti-PD-1 monoclonal antibody) in combination with chemotherapy has been approved for first-line treatment of metastatic NSCLC. Additionally, atezolizumab (an anti-PD-L1 monoclonal antibody) combined with chemotherapy has also received FDA approval for certain types of NSCLC. These treatments are similar to the combination of Fianlimab and Cemiplimab with chemotherapy being studied in the trial, as they all involve the use of immune checkpoint inhibitors to enhance the efficacy of traditional cytotoxic agents.

What other types of research exist?

Promising alternatives to the combination of Fianlimab and Cemiplimab with chemotherapy for NSCLC patients include: 1) Nivolumab (Anti-PD-1) combined with Ipilimumab (Anti-CTLA-4), which has shown efficacy in various cancers including NSCLC. 2) Pembrolizumab (Anti-PD-1) combined with chemotherapy, which is already approved for first-line treatment of metastatic NSCLC. 3) Novel combinations of immune checkpoint inhibitors with targeted therapies such as VEGF inhibitors (e.g., Bevacizumab) or other novel agents targeting specific mutations or pathways in NSCLC.

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Monoclonal Antibodies

Fianlimab + Cemiplimab + Chemotherapy for Non-Small Cell Lung Cancer

Phase 2 & 3

Recruiting

Research Sponsored by Regeneron Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.

Availability of an archival or on-study formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol

Must not have

Patients with tumors tested positive for actionable estimated glomerular filtration rate (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS oncogene 1 (ROS1) fusions, as described in the protocol.

History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial is testing a new drug called fianlimab with cemiplimab and chemotherapy in patients with advanced lung cancer. The goal is to see if this combination is more effective than current treatments. The new drugs help the immune system fight cancer, while chemotherapy attacks the cancer cells directly.

Who is the study for?

Adults with advanced non-small cell lung cancer (NSCLC) who haven't had systemic treatment for recurrent or metastatic NSCLC. They must have a performance status ≤1, indicating they are relatively active and can care for themselves. Participants need to have measurable lung cancer lesions and adequate organ function. Those with certain gene mutations, recent immune suppression treatments, untreated brain metastases, significant autoimmune disease, or prior specific therapies are excluded.

What is being tested?

The trial is testing the effectiveness of fianlimab combined with cemiplimab and chemotherapy versus just cemiplimab and chemotherapy in treating advanced NSCLC. It will also examine side effects, drug levels in blood over time, potential antibody development against the drugs, and any impact on quality of life.

What are the potential side effects?

Potential side effects include reactions related to the immune system affecting various organs which could lead to inflammation issues; infusion-related reactions during administration; fatigue; digestive problems like nausea or diarrhea; changes in blood counts leading to increased risk of infections or bleeding.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active and can carry on all pre-disease activities without restriction.

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I have a tumor sample available that was taken before any treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My tumor has EGFR mutations, ALK translocations, or ROS1 fusions.

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I have had lung conditions but not active lung inflammation needing strong medication in the last 5 years.

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I have a known primary immunodeficiency disorder.

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I have an autoimmune disease treated with immunosuppressants in the last 2 years.

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I don't have active brain tumors or untreated spinal issues, or they've been treated and I've been stable for 2 weeks without steroids.

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I have not had encephalitis, meningitis, or uncontrolled seizures in the last year.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR) as assessed by blinded independent review committee (BICR) using RECIST 1.1

Overall Survival (OS)

Secondary study objectives

Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)

Change from baseline in patient-reported cough per EORTC QLQ-LC13

Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13

+36 more

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase 3 - Arm CExperimental Treatment6 Interventions

Randomized 1:1 cemiplimab + platinum-doublet chemotherapy + placebo

Group II: Phase 3 - Arm A or BExperimental Treatment6 Interventions

Randomized 1:1 fianlimab (chosen dose) + cemiplimab + platinum-doublet chemotherapy

Group III: Phase 2 - Arm CExperimental Treatment6 Interventions

Randomized 1:1:1 cemiplimab + platinum-doublet chemotherapy + placebo

Group IV: Phase 2 - Arm BExperimental Treatment6 Interventions

Randomized 1:1:1 fianlimab (lower dose) + cemiplimab + platinum-doublet chemotherapy

Group V: Phase 2 - Arm AExperimental Treatment6 Interventions

Randomized 1:1:1 fianlimab (higher dose) + cemiplimab + platinum-doublet chemotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cisplatin

2013

Completed Phase 3

~3120

Carboplatin

2014

Completed Phase 3

~6120

cemiplimab

2016

Completed Phase 2

~910

Pemetrexed

2014

Completed Phase 3

~5550

Paclitaxel

2011

Completed Phase 4

~5450

Placebo

1995

Completed Phase 3

~2670

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors and chemotherapy. Immune checkpoint inhibitors, such as Cemiplimab (an anti-PD-1 monoclonal antibody) and investigational drugs like Fianlimab (an anti-LAG-3 monoclonal antibody), work by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. Chemotherapy involves cytotoxic agents like paclitaxel and carboplatin, which kill rapidly dividing cancer cells by interfering with their DNA replication. These treatments are crucial for NSCLC patients as they can improve survival rates and quality of life by targeting cancer cells through different mechanisms, potentially leading to more effective and comprehensive cancer control.

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies.Cetuximab and other anti-epidermal growth factor receptor monoclonal antibodies in the treatment of non-small cell lung cancer.