Fianlimab + Cemiplimab for Non-Small Cell Lung Cancer

Recruiting at 175 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Never smoked, Brain metastases, 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

Duration: Up to 136 weeks

850 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new drug combination, fianlimab and cemiplimab (an immunotherapy drug), for treating advanced non-small cell lung cancer (NSCLC). Researchers aim to determine if this combination outperforms cemiplimab alone. The trial also examines potential side effects, drug levels in the blood over time, and whether the body produces antibodies against the drugs. Suitable participants have advanced NSCLC that has not been treated with systemic therapy and have a specific protein (PD-L1) in their tumors. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in lung cancer treatment.

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, if you are on corticosteroid therapy or have received certain systemic therapies recently, you may need to adjust or stop those medications before enrolling.

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

Research has shown that the combination of fianlimab and cemiplimab is generally safe and well-tolerated. In studies, patients taking these drugs did not encounter any unexpected safety problems. The safety of this combination aligns with earlier reports for these drugs.

Cemiplimab alone also has a well-established safety record. Other studies found that less than 3% of patients experienced immune-related lung issues, such as pneumonitis (lung inflammation), a known side effect of similar treatments.

Overall, both the combination of fianlimab and cemiplimab, as well as cemiplimab alone, have demonstrated manageable safety in studies so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for non-small cell lung cancer, which typically includes chemotherapy or targeted therapies like EGFR and ALK inhibitors, the combination of fianlimab and cemiplimab acts on the immune system. Fianlimab is a novel agent that targets LAG-3, a protein that helps tumors evade the immune system, while cemiplimab is a PD-1 inhibitor that unleashes T-cells to attack cancer. Researchers are excited because this dual immune checkpoint blockade could potentially enhance the immune response against tumors more effectively than existing treatments. By targeting these distinct pathways, this combination therapy offers a new angle in the fight against lung cancer.

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

Research has shown that cemiplimab, one of the treatments in this trial, can significantly improve survival rates for patients with advanced non-small cell lung cancer (NSCLC) when used alone. Patients treated with cemiplimab lived for a median of 21.1 months, compared to 12.9 months for those who received only chemotherapy. This makes cemiplimab a promising standalone treatment option.

Additionally, early research suggests that combining fianlimab with cemiplimab, as tested in other arms of this trial, might enhance the body's ability to fight cancer. This combination targets different parts of the immune system, potentially increasing its effectiveness. These initial findings support further testing of this combination for treating NSCLC. ^{3 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 advanced non-small cell lung cancer (NSCLC) who haven't had prior treatments for metastatic disease, have high PD-L1 levels (≥50%), and can provide a tumor tissue sample. They should have at least one measurable lesion, good organ function, and an ECOG performance status of ≤1. Excluded are those needing significant steroid treatment recently, with certain immune conditions or untreated brain metastases.

Inclusion Criteria

My organs and bone marrow are working well.

I can provide a tumor tissue sample that has not been treated since its collection.

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

Exclusion Criteria

I haven't had encephalitis, meningitis, or uncontrolled seizures in the last year.

I haven't taken high-dose steroids for immune suppression in the last 14 days.

I do not have an active autoimmune disease that needed strong medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the combination of fianlimab and cemiplimab or cemiplimab monotherapy

Up to 136 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

• Cemiplimab
• Fianlimab
• Placebo

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

How Is the Trial Designed?

Group I: C: cemiplimab monotherapy+placebo Experimental Treatment 2 Interventions

Phase 2 and Phase 3

Group II: B: fianlimab+cemiplimab Experimental Treatment 2 Interventions

Phase 2: fianlimab (LD) Phase 3: fianlimab (chosen dose)

Group III: A: fianlimab+cemiplimab Experimental Treatment 2 Interventions

Phase 2: fianlimab (HD) Phase 3: fianlimab (chosen dose)

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

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]

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]

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]

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]

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 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]

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 offers significantly longer time in both preprogression and postprogression health states compared to pembrolizumab and chemotherapy, indicating its potential for better patient outcomes in advanced non-small cell lung cancer.

The cost-effectiveness analysis shows that cemiplimab is a viable first-line treatment option, with incremental cost-effectiveness ratios of $68,254 per QALY compared to pembrolizumab and $89,219 per QALY compared to chemotherapy, making it likely to be cost-effective within common willingness-to-pay thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50. Kuznik, A., Smare, C., Chen, CI., 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. libtayohcp.com libtayohcp.com/nsclc/efficacy/monotherapy/response-rates

Efficacy overview - LIBTAYO® (cemiplimab-rwlc) Efficacy Overview ; OS. Median, months (95% CI) · 22.1 (17.7-NE). 14.3 (11.7-19.2). HR (95% CI) · 0.68 (0.53-0.87) ; PFS per BICR. Median, months (95% CI) · 6.2 (4.5 ...

3. ajmc.com ajmc.com/view/survival-outcomes-in-advanced-nsclc-improved-with-use-of-cemiplimab

Survival Outcomes in Advanced NSCLC Improved With ... The EMPOWER-Lung 3 trial showed a median overall survival of 21.1 months with cemiplimab versus 12.9 months with chemotherapy alone.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20572

Evaluating the safety and effectiveness of cemiplimab in ... This observational study (NCT06269133) will assess the RW safety and effectiveness of first-line (1L) treatment of aNSCLC with cemiplimab in combination with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12051739/

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)

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40118215/

Five-Year Outcomes of EMPOWER-Lung 1 The five-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and nonsquamous ...

7. libtayohcp.com libtayohcp.com/nsclc/safety/monotherapy/follow-up-data

LIBTAYO safety profile in EMPOWER-Lung 1: 3-year data 1 Immune-mediated pneumonitis occurred in 2.6% (33/1281) of patients receiving LIBTAYO, including Grade 4 (0.3%), Grade 3 (0.6%), and Grade 2 (1.6%). Pneumonitis ...

8. jto.org jto.org/article/S1556-0864%2825%2900178-9/fulltext

Five-Year Outcomes of EMPOWER-Lung 1 The five-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and nonsquamous ...