Cemiplimab + Fianlimab for Lung Cancer

(N-PLANC Trial)

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, Organ transplant, others

Stay on Your Current Meds You can continue your current medications while participating

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: 8

Duration: 9 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining two immunotherapy drugs, cemiplimab and fianlimab, in shrinking non-small cell lung cancer (NSCLC) tumors before surgery. The goal is to enhance the body's immune response to attack and potentially reduce the cancer, thereby making surgery more effective. Individuals with stage IB-IIIB NSCLC, whose tumors can be surgically removed and have a PD-L1 expression of at least 1%, may be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days 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 has shown that the combination of cemiplimab and fianlimab was safe in earlier studies. Patients generally tolerated the treatment well, and it showed promise in fighting tumors. While side effects can occur, they are usually manageable and not severe for most people.

These results come from studies on other cancers, such as melanoma. The current trial tests this treatment for lung cancer, which might yield different outcomes. However, existing research suggests similar safety can be expected. Participants should always discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cemiplimab and fianlimab for lung cancer because it represents a novel approach to treatment. Unlike traditional therapies that might focus on chemotherapy or targeting specific cancer growth pathways, this combination uses two immune checkpoint inhibitors. Cemiplimab targets PD-1, and fianlimab targets LAG-3, both of which are proteins that cancer cells exploit to evade the immune system. By blocking these proteins, the treatment aims to enhance the body's natural immune response to fight cancer more effectively. This dual-action mechanism offers a promising new angle in lung cancer treatment, potentially improving outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

Research has shown that using cemiplimab and fianlimab together may help treat non-small cell lung cancer (NSCLC). In this trial, participants will receive both cemiplimab and fianlimab as part of the treatment regimen. Cemiplimab alone has effectively targeted this type of cancer, and adding fianlimab enhances the immune system's ability to fight cancer. Early results suggest this combination is safe and can shrink tumors. This approach aims to make cancer cells easier to attack, potentially improving outcomes before surgery. ^{1 2 6 7 8}

Who Is on the Research Team?

Kaushal Parikh, MBBS

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with stage IB-IIIB non-small cell lung cancer. Participants should be suitable candidates for surgery and have not undergone neoadjuvant therapy yet. Specific eligibility details are not provided, but typically include being over a certain age, having adequate organ function, and no other serious medical conditions.

Inclusion Criteria

Negative pregnancy test done ≤ 8 days prior to registration

Pathologic status of lymph nodes must be known

My tumor is larger than 7 cm but is classified as T4 only because of its size.

Exclusion Criteria

My cancer cannot be removed by surgery or has spread.

I do not have an uncontrolled HIV, HBV, or HCV infection or an immunodeficiency.

Pregnant persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cemiplimab and fianlimab intravenously every 21 days for up to 3 cycles

9 weeks

3 visits (in-person)

Surgery

Participants may undergo standard of care surgery post-treatment

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab

Trial Overview The trial is testing the effectiveness of combining two monoclonal antibodies, cemiplimab and fianlimab, before surgery as a treatment approach. It aims to see if this combination can better eliminate tumor cells compared to current standard pre-surgery treatments in NSCLC patients.

How Is the Trial Designed?

Group I: Treatment (cemiplimab, fianlimab) Experimental Treatment 5 Interventions

Patients receive cemiplimab IV over 30 minutes on day 1 of each cycle and fianlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI during screening, tissue sample collection on study and blood sample collection on study and follow-up. Patients may undergo SOC surgery post-treatment.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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]

Cemiplimab significantly improves overall survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 levels, adding 0.546 quality-adjusted life years (QALYs) compared to chemotherapy.

The treatment is considered cost-effective, with an incremental cost-effectiveness ratio of $40,390 per QALY gained, and a 100% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50. Wang, L., Peng, Y., Zeng, X., et al.[2021]

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]

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]

A study involving 132 patients with non-small cell lung cancer developed prediction models using radiomic and clinical features to identify those likely to benefit from anti-PD-1/PD-L1 therapy, achieving a high prediction accuracy with an AUC-ROC of 87%.

The radiomic model effectively predicted progression-free survival, indicating that imaging features can help select patients who may respond well to immunotherapy, potentially reducing the risk of unnecessary treatment and associated immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer. Schroeder, KE., Acharya, L., Mani, H., et al.[2023]

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]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

In a meta-analysis of 16 clinical trials involving 6208 patients with non-small cell lung cancer, the overall incidence of immune-related adverse events (irAEs) was found to be 22%, with a higher rate of severe irAEs (4%) associated with PD-1 inhibitors compared to PD-L1 inhibitors.

The most common organ-specific irAEs occurred in the endocrine system, skin, pulmonary tract, and gastrointestinal tract, with pneumonitis being the leading cause of death among the 14 patients (0.34%) who died due to irAEs, highlighting the importance of monitoring and managing these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis. Sun, X., Roudi, R., Dai, T., et al.[2020]

Citations

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A phase 2/3 study of fianlimab plus cemiplimab versus ... This is a randomized, double-blind, Phase 2/3 study (NCT05785767) to evaluate fianlimab + cemiplimab versus cemiplimab monotherapy as first-line treatment in ...

2. 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 ...

3. 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 ...

4. jto.org jto.org/article/S1556-0864(24)01585-5/fulltext

P4.11D.09 Fianlimab-Based Combination Therapies in ... Cemiplimab has shown promising clinical efficacy in patients with non-small cell lung cancer (NSCLC) and no actionable mutations, alone (programmed cell death ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01143

A Trial to Learn How the Combination of Fianlimab With ... 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 ...

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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 ...

7. onclive.com onclive.com/view/fianlimab-cemiplimab-demonstrates-persistent-activity-in-advanced-melanoma-independent-of-lag-3-and-pd-l1-status

Fianlimab/Cemiplimab Demonstrates Persistent Activity in ... Fianlimab plus cemiplimab demonstrated persistent and significant clinical activity in patients with advanced melanoma.

8. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab-shows

Fianlimab (LAG-3 inhibitor) Combined with Libtayo® ... Data demonstrate objective response rates from 56% to 63% across three independent cohorts of advanced melanoma patients.