Fianlimab + Cemiplimab + Chemotherapy for Lung Cancer

Recruiting at 185 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunotherapy, Chemotherapy, Radiotherapy

Disqualifiers: Metastatic disease, EGFR mutations, 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

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two experimental drugs, fianlimab and cemiplimab, with chemotherapy to evaluate their effectiveness for individuals with non-small cell lung cancer that can be surgically removed. Researchers aim to determine if this new combination surpasses the current standard treatment. They will also monitor side effects, how the body processes the drugs, and whether the body develops antibodies that could impact the treatment. This study suits those recently diagnosed with stage II to IIIB non-small cell lung cancer, with no signs of disease spreading. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining fianlimab and cemiplimab with chemotherapy has been safe in earlier studies. These studies found that using fianlimab and cemiplimab together was effective and generally safe, with most side effects being manageable.

Evidence also indicates that cemiplimab is safe. It has been used with chemotherapy in other studies, which showed good long-term results and improved survival for lung cancer patients. Patients can usually tolerate cemiplimab and chemotherapy together quite well.

Platinum-doublet chemotherapy is a standard treatment for lung cancer, and its safety is well-established. Doctors widely use and understand it.

Overall, while any treatment can have side effects, research suggests these drugs are relatively safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lung cancer, which often rely on chemotherapy and radiation, the combination of Fianlimab and Cemiplimab, alongside chemotherapy, offers a novel approach. Fianlimab is a new type of drug known as an anti-LAG-3 antibody, which works by boosting the immune system’s ability to fight cancer cells, something traditional options don't do. Cemiplimab, on the other hand, is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells more effectively. Researchers are excited because these treatments could potentially enhance the body's natural defenses against cancer, offering hope for more effective and targeted therapy.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare different treatment combinations for non-small cell lung cancer (NSCLC). Research has shown that combining the drugs fianlimab and cemiplimab with chemotherapy may be effective. In this trial, participants in Arm B will receive a high dose of fianlimab with cemiplimab and platinum doublet chemotherapy, while those in Arm C will receive a low dose of fianlimab with cemiplimab and platinum doublet chemotherapy. Arm A will involve a placebo with cemiplimab and platinum doublet chemotherapy. Studies have found that cemiplimab, when used with chemotherapy, can more than double the chances of living for five years compared to using chemotherapy alone. Fianlimab, both on its own and with cemiplimab, has shown early signs of fighting tumors, suggesting it could be a strong ally against NSCLC. Initial trials indicated that these drug combinations are safe and may help shrink or control the cancer. These findings offer hope for using these drugs together to treat NSCLC successfully. ^{1 5 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cemiplimab
• Cisplatin
• Fianlimab
• Paclitaxel
• Pemetrexed

Trial Overview 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.

How Is the Trial Designed?

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)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

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. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Inhibitory antibodies targeting PD-1 and PD-L1 have significantly improved outcomes for patients with metastatic non-small cell lung cancer (NSCLC), especially when combined with platinum-based chemotherapy, leading to better response rates and increased survival compared to chemotherapy alone.

Pembrolizumab and atezolizumab are approved as first-line treatments for most newly diagnosed metastatic NSCLC patients, demonstrating the potential for immunotherapy to enhance treatment effectiveness, even in specific patient populations with certain genetic mutations.

NCBI (Pubmed)

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. Pacheco, JM., Camidge, DR., Doebele, RC., et al.[2023]

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]

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]

At 35 months of follow-up, patients with advanced non-small-cell lung cancer and high PD-L1 expression treated with cemiplimab had a median overall survival of 26.1 months, significantly better than the 13.3 months for those receiving chemotherapy, indicating a strong survival benefit from cemiplimab.

The addition of chemotherapy to cemiplimab after disease progression resulted in a median overall survival of 15.1 months, suggesting that this combination could be an effective second-line treatment option for patients with advanced non-small-cell lung cancer.

NCBI (Pubmed)

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. Özgüroğlu, M., Kilickap, S., Sezer, A., 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]

In the EMPOWER-Lung 1 trial, cemiplimab significantly improved overall survival compared to platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression (≥50%).

Patients receiving cemiplimab reported better quality of life and functioning, with a lower risk of definitive deterioration in symptoms such as dyspnea, cough, and fatigue, indicating that cemiplimab not only extends survival but also enhances the patient's overall well-being.

NCBI (Pubmed)

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. Gümüş, M., Chen, CI., Ivanescu, C., et al.[2023]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

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. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

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. Isla, D., Sánchez, A., Casal, J., et al.[2023]

In patients with advanced non-small-cell lung cancer (NSCLC) and high PD-L1 expression (≥50%), cemiplimab showed significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared to pembrolizumab, based on a systematic review and network meta-analysis of randomized-controlled trials.

Cemiplimab demonstrated comparable overall survival (OS) and similar safety profiles to pembrolizumab, indicating it is a viable first-line treatment option for this patient population.

NCBI (Pubmed)

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. Freemantle, N., Xu, Y., Wilson, FR., et al.[2022]

Citations

1. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11647203/

First-in-Human Dose-Escalation Study of Fianlimab, an ... Fianlimab as monotherapy and in combination with cemiplimab demonstrated acceptable safety and preliminary antitumor activity, which is generally consistent ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05800015

Study Details | NCT05800015 | A Trial to Learn How the ... The aim of the study is to see how effective the combination of fianlimab, cemiplimab, and chemotherapy is for treating advanced NSCLC, in comparison with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8663

A phase 2/3 study of fianlimab plus cemiplimab versus ... In Phase 3, the primary endpoint is OS in patients receiving fianlimab + cemiplimab versus cemiplimab monotherapy. Secondary endpoints are ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06161441

Study Details | NCT06161441 | A Trial to Learn if the ... 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 ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8117

Phase 2 peri-operative study of fianlimab + cemiplimab + ... The aim of this study is to investigate the efficacy and safety of fianlimab + cemiplimab + chemotherapy versus cemiplimab + chemotherapy as peri-operative ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424015557

P4.07D.03 Phase 2 Peri-Operative Study of Fianlimab ... In a Phase 1 study (NCT03005782), fianlimab + cemiplimab showed promising clinical activity with durable responses and an acceptable risk-benefit profile in ...

8. kumc.trialstoday.org kumc.trialstoday.org/trial/NCT06161441

A Trial to Learn if the Combination of Fianlimab ... A Trial to Learn if the Combination of Fianlimab, Cemiplimab, and Chemotherapy is Safe and Works Better Than the Combination of Cemiplimab ...