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

Recruiting at 96 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

Trial Summary

What is the purpose of this trial?

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.

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.

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

Research shows that cemiplimab, a PD-1 inhibitor, is effective in treating non-small cell lung cancer, especially when combined with chemotherapy. Additionally, cisplatin-based chemotherapy regimens have been shown to reduce mortality and improve survival in patients with non-small cell lung cancer. ^{1 2 3 4 5}

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

Pemetrexed, when combined with cisplatin, has shown a favorable safety profile with less frequent and severe side effects compared to other treatments for non-small cell lung cancer. Cemiplimab, used in combination with chemotherapy, is also part of approved treatments for this condition, indicating it has been evaluated for safety in humans. ^{2 5 6 7 8}

What makes the drug combination of Fianlimab, Cemiplimab, and Chemotherapy unique for treating non-small cell lung cancer?

This treatment is unique because it combines Fianlimab and Cemiplimab, which are newer immunotherapy drugs, with traditional chemotherapy agents like Cisplatin and Paclitaxel, potentially enhancing the immune system's ability to fight cancer while also directly targeting cancer cells. ^{1 3 9 10 11}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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-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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. [2018]

2. 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]

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

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

4. 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]

5. 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]

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

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

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

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

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

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

9. France pubmed.ncbi.nlm.nih.gov

[Stage IV NSCLC. Place of chemotherapy]. [2013]

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

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

11. United States 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. [2018]