Fianlimab + Cemiplimab + Chemotherapy for Lung Cancer

Recruiting in Palo Alto (17 mi)

+51 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunotherapy, Chemotherapy, Radiotherapy

Disqualifiers: Metastatic disease, EGFR mutations, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called fianlimab (also called REGN3767) with two other medications called cemiplimab and platinum-doublet chemotherapy, individually called a "study drug" or collectively called "study drugs", when combined in this study. The study is being conducted in patients who have resectable stage II to IIIB (N2) non-small cell lung cancer (NSCLC) that can be treated with surgery. The aim of the study is to see how effective the combination of fianlimab, cemiplimab, and chemotherapy is in comparison with cemiplimab and chemotherapy as peri-operative therapy in participants with NSCLC. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much of each study drug is in the blood at different times * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects) * How administering the study drugs might affect quality of life

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it does exclude those who have had certain cancer treatments in the past 3 years, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Fianlimab + Cemiplimab + Chemotherapy for Lung Cancer?

Research shows that cemiplimab, when used alone or with chemotherapy, improves survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 levels. Combining immunotherapies like cemiplimab with chemotherapy has led to better response rates and longer survival compared to chemotherapy alone.

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Is the combination of Fianlimab, Cemiplimab, and chemotherapy safe for humans?

Cemiplimab, used in combination with chemotherapy, has been studied for safety in treating non-small cell lung cancer and other cancers. Common side effects include immune-related reactions, which can affect the skin, liver, lungs, and other organs. These treatments are generally considered safe, but they can have significant side effects that need to be managed by healthcare professionals.

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What makes the drug combination of Fianlimab, Cemiplimab, and chemotherapy unique for lung cancer treatment?

The combination of Fianlimab and Cemiplimab with chemotherapy is unique because it leverages the immune system by using PD-1 inhibitors, like Cemiplimab, to enhance the body's ability to fight cancer cells, potentially offering improved survival benefits compared to chemotherapy alone, especially in patients with high PD-L1 expression.

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Eligibility Criteria

Adults with resectable stage II to IIIB (N2) non-small cell lung cancer, confirmed by tests and without distant metastases. Participants must be physically fit enough for surgery (ECOG status 0 or 1), have proper organ function, and an evaluable PD-L1 IHC result.

Inclusion Criteria

My tests show swollen lymph nodes in my chest, and I've had a biopsy as required.

My recent tests show no signs of cancer spread beyond its original site.

My lung cancer is in stage II to IIIB and can be surgically removed.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive fianlimab, cemiplimab, and platinum-doublet chemotherapy or placebo with cemiplimab and chemotherapy

8-12 weeks

Surgery

Participants undergo surgical resection of the tumor

1 week

Adjuvant Treatment

Participants receive fianlimab and cemiplimab or placebo with cemiplimab

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Participant Groups

The trial is testing the safety and effectiveness of a new drug combo: fianlimab, cemiplimab, plus chemotherapy versus just cemiplimab with chemotherapy. It's given before surgery to see if it works better for NSCLC.

Group I: Arm C Experimental Treatment 6 Interventions

Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab

Group II: Arm B Experimental Treatment 6 Interventions

Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab

Group III: Arm A Experimental Treatment 6 Interventions

Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mid Florida Hematology and Oncology Center Orange City, FL

Virginia Cancer Care Specialist, PC Fairfax, VA

Clermont Oncology Center Clermont, FL

Mid-Florida Hematology & Oncology Centers, PA Orange City, FL

More Trial Locations

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals Lead Sponsor

References

1. New Zealand 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. [2023] In metastatic non-small cell lung cancer (NSCLC), tumors that do not harbor driver mutations in EGFR or gene fusions in ALK and ROS, PD-1 and PD-L1 inhibitors have become a cornerstone in first line treatment, either as monotherapy or in combination with chemotherapy. This paper reviews cemiplimab-rwlc, the third PD-1/L1 inhibitor to be approved in the setting for first line treatment in NSCLC, as monotherapy or in combination therapy with chemotherapy, to provide a perspective on the subtle differences in patient population for the cemiplimab studies and consideration of its primary and subgroup results in the context of first line therapies for NSCLC.

2. England 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. [2022] We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer. [2023] Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data.

4. United States pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. [2023] In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants.

5. England pubmed.ncbi.nlm.nih.gov

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. [2023] Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.

6. England pubmed.ncbi.nlm.nih.gov

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50. [2022] Label="Background" NlmCategory="UNASSIGNED">For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020.

7. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019] Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.

8. United States pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. [2021] To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression.

9. England pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022] Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non-small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC.

10. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. [2023] There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups.