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

Recruiting at 115 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: 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 108 weeks

950 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment combination for people with advanced non-small cell lung cancer (NSCLC). It tests fianlimab (an experimental drug) with cemiplimab and chemotherapy to determine if this combination is more effective than cemiplimab with chemotherapy alone. Researchers also assess any side effects and potential improvements in quality of life. Individuals with advanced NSCLC who have not received other treatments for their condition may be suitable candidates for this trial. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, providing patients access to potentially groundbreaking therapy.

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 before joining the trial. 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 shows that the combination of fianlimab, cemiplimab, and chemotherapy is under study for safety and effectiveness in treating advanced non-small cell lung cancer (NSCLC). Previous studies have found that cemiplimab with chemotherapy can extend patient survival and is generally well-tolerated. Most side effects were manageable, though some patients experienced low blood cell counts, tiredness, and nausea.

Less information exists about fianlimab because it remains under investigation. However, in current trials testing fianlimab with cemiplimab and chemotherapy, researchers closely monitor safety. Early results suggest that this combination might have side effects similar to those seen with cemiplimab and chemotherapy alone.

The studies are in advanced stages, indicating that earlier research has shown a reasonable safety profile. This suggests that while side effects are possible, they are being carefully studied and managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of combining fianlimab and cemiplimab with chemotherapy for non-small cell lung cancer (NSCLC) because these treatments have unique mechanisms that may enhance effectiveness. Unlike traditional treatments that primarily focus on chemotherapy alone, fianlimab and cemiplimab are immunotherapies that boost the body's immune response to target and kill cancer cells more effectively. Fianlimab is a novel anti-LAG-3 antibody, while cemiplimab is an anti-PD-1 antibody, both of which work by unleashing the immune system to better recognize and attack cancer cells. This combination could potentially offer a more powerful and targeted attack against NSCLC, potentially improving outcomes compared to standard chemotherapy regimens.

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

Research has shown that combining cemiplimab with a type of chemotherapy called platinum-doublet yields promising results for treating advanced non-small cell lung cancer (NSCLC). Studies have found that this combination can significantly increase survival rates. Specifically, patients receiving cemiplimab and chemotherapy more than doubled their chances of surviving five years compared to those who did not receive this combination.

In this trial, some participants will receive cemiplimab with platinum-doublet chemotherapy, while others will receive an additional treatment with fianlimab. Research on fianlimab is ongoing, as it uniquely helps the immune system fight cancer cells more effectively. Early results suggest that adding fianlimab to the cemiplimab and chemotherapy treatment may enhance its effectiveness. However, further research is needed to confirm these initial findings. ^{1 2 4 5 6}

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 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.

Inclusion Criteria

In phase 2, patients need to have their PD-L1 expression tested by an accredited lab. In phase 3, patients need a valid PD-L1 test from a central lab.

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

My organs and bone marrow are working well.

Exclusion Criteria

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

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

I have not had systemic therapies except for some exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fianlimab, cemiplimab, and chemotherapy or cemiplimab and chemotherapy

Up to 108 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Extension

Participants may continue to be monitored for long-term outcomes and survival

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Cisplatin
• Fianlimab
• Paclitaxel
• Pemetrexed

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase 3 - Arm C Experimental Treatment 6 Interventions

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

Group II: Phase 3 - Arm A or B Experimental Treatment 6 Interventions

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

Group III: Phase 2 - Arm C Experimental Treatment 6 Interventions

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

Group IV: Phase 2 - Arm B Experimental Treatment 6 Interventions

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

Group V: Phase 2 - Arm A Experimental Treatment 6 Interventions

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

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

In a phase II study involving 53 patients with advanced non-small cell lung cancer, the combination of cetuximab, paclitaxel, and carboplatin resulted in a response rate of 57%, indicating significant clinical activity.

The treatment was well tolerated with manageable toxicities, including rash and neutropenia, and no grade 5 toxicities reported, suggesting a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel, carboplatin, and cetuximab as first line treatment, for patients with advanced non-small cell lung cancer (NSCLC): results of OPN-017. Borghaei, H., Langer, CJ., Millenson, M., et al.[2018]

Five new cytotoxic drugs have been introduced for treating non-small-cell lung cancer (NSCLC), showing comparable activity to cisplatin when used alone, and improved survival when combined with cisplatin.

Randomized studies indicate that these newer drugs not only enhance survival rates but also reduce side effects compared to older chemotherapy regimens, suggesting they are valuable options for patients, including those previously treated with platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for non-platinum chemotherapy in advanced NSCLC. Murren, JR.[2022]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

Cisplatin combined with either a vinca alkaloid or etoposide is highly effective in reducing mortality for patients with non-small cell lung cancer, as shown in meta-analyses comparing chemotherapy to supportive care.

Recent studies indicate that combining cisplatin-based chemotherapy with new agents and radiotherapy can significantly prolong survival and improve outcomes for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. Shinkai, T., Saijo, N.[2018]

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]

Cisplatin-based chemotherapy significantly improves survival and symptom control in stage IV non-small cell lung cancer patients with good performance status, suggesting its effectiveness as a primary treatment option.

Combination regimens including cisplatin and at least one other active drug (like ifosfamide or gemcitabine) are recommended, with four to six cycles proposed for patients who respond well, while non-platinum options can be considered for those unable to tolerate platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stage IV NSCLC. Place of chemotherapy]. Meert, AP.[2013]

Recent advancements in treating non-small cell lung cancer (NSCLC) have led to the development of newer chemotherapeutic agents, achieving single-agent response rates of 20% or higher.

The combination of carboplatin and paclitaxel has shown promising results, with response rates as high as 62%, and ongoing Phase III trials are exploring its role in NSCLC treatment alongside newer agents and biologically based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of paclitaxel/carboplatin in advanced non-small cell lung cancer. Bonomi, P.[2015]

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]

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]

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. 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 ...

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

Survival Outcomes in Advanced NSCLC Improved With ... The use of cemiplimab with chemotherapy showed durable improvements in survival outcomes for non-small cell lung cancer (NSCLC) after 5 years.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9671806/

Cemiplimab plus chemotherapy versus ... - PubMed Central Results from EMPOWER-Lung 3 demonstrate increased overall survival with cemiplimab plus platinum-doublet chemotherapy compared to cemiplimab as ...

5. lungcancerstoday.com lungcancerstoday.com/post/asco-2025-dr-alexi-archambault-discusses-the-first-line-combination-of-cemiplimab-and-chemotherapy-for-nsclc

ASCO 2025: Dr. Alexi Archambault Discusses the First- ... Share research insights from her study on the safety and effectiveness of cemiplimab plus platinum-doublet chemotherapy by demographic characteristics.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06161441

Study Details | NCT06161441 | A Trial to Learn if the ... ... Safe and Works Better Than the Combination of Cemiplimab and Chemotherapy in Adult Patients With Non-Small Cell Lung Cancer That Can be Treated With Surgery.