Sarilumab + Cemiplimab for Lung Cancer

Overseen By Xiuning Le, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: EGFR TKI

Must not be taking: Antibiotics, Antivirals, Antifungals, others

Disqualifiers: Autoimmune disorders, Diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

56 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if the combination of sarilumab (also called Kevzara) and cemiplimab can help to control EGFR- or LKB1/STK11-mutant NSCLC.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination Sarilumab and Cemiplimab for lung cancer?

Cemiplimab has been shown to improve survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression, making it an effective option for this type of cancer. ^{1 2 3 4 5}

Is cemiplimab safe for use in humans?

Cemiplimab has been studied in clinical trials for non-small cell lung cancer and cutaneous squamous cell carcinoma, showing common side effects and safety issues typical of immunotherapy drugs. It is generally considered safe, but like other immunotherapies, it can cause side effects related to immune system activation. ^{1 2 3 6 7}

What makes the drug combination of Sarilumab and Cemiplimab unique for lung cancer treatment?

The combination of Sarilumab and Cemiplimab for lung cancer is unique because it pairs an anti-inflammatory drug (Sarilumab) with an immunotherapy drug (Cemiplimab), which is a PD-1 inhibitor that enhances the immune system's ability to fight cancer. This combination may offer a novel approach by potentially reducing inflammation while boosting the immune response against cancer cells. ^{1 2 3 7 8}

Research Team

Xiuning Le, M.D., Ph.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with advanced non-squamous, non-small cell lung cancer (NSCLC) and specific mutations (EGFR or LKB1). They may have had up to three prior treatments but must not be pregnant, breastfeeding, or have severe diseases. Participants need functioning major organs and no recent surgeries. Men and women must agree to use contraception.

Inclusion Criteria

I am a man who can father children and will use birth control during and 3 months after the study.

Patients who meet eligibility criteria to either Cohort A or B will be allowed to enroll to the run-in cohort.

My NSCLC has specific EGFR mutations confirmed by a certified test.

Exclusion Criteria

I have skin ulcers that are healing or not yet healed.

I have not received a live vaccine in the last 3 months.

I do not have serious heart issues like severe heart failure or uncontrolled heart rhythm problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Evaluate the safety of sarilumab and cemiplimab combination in metastatic lung cancer patients

4-6 weeks

Treatment

Participants receive sarilumab and cemiplimab to assess efficacy in EGFR- or LKB1/STK11-mutant NSCLC

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Cemiplimab
• Sarilumab

Trial Overview The trial is testing the effectiveness of combining two drugs: Sarilumab (Kevzara) and Cemiplimab for NSCLC patients with certain genetic mutations. It aims to control the disease by using these medications together in participants who meet specific genetic criteria.

Participant Groups

Group I: Cohort B: LKB1-mutant cohort Experimental Treatment 2 Interventions

Each cohort is planned for 30 Participants with a total of 60 Participants. Participants who are treated in Run-In safety cohort can also be evaluated for efficacy in the molecularly define cohort A or B.

Group II: Cohort A : EGFR-mutant cohort Experimental Treatment 2 Interventions

Each cohort is planned for 30 Participants with a total of 60 Participants. Participants who are treated in Run-In safety cohort can also be evaluated for efficacy in the molecularly define cohort A or B.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Regeneron Pharmaceuticals

Industry 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

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]

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]

Cemiplimab showed the most favorable overall survival (OS) compared to other PD-1/PD-L1 inhibitors and chemotherapy, indicating it may be the best option for treating non-small cell lung cancer (NSCLC) patients based on a network meta-analysis of multiple studies.

All PD-1/PD-L1 inhibitors, including cemiplimab, had fewer treatment-related adverse events (TRAEs) compared to chemotherapy, suggesting a better safety profile for these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies. Jiang, M., Liu, C., Ding, D., 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 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-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]

Cemiplimab, a PD-1 inhibitor, demonstrated an objective response rate of 25% in patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone treatment, indicating its potential effectiveness in this challenging patient population.

The treatment was generally well-tolerated, although 60% of patients experienced severe treatment-emergent adverse events, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. Moreno, V., Garrido, P., Papadopoulos, KP., et al.[2021]

References

1. 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]

2. 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]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies. [2023]

5. United States 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. [2023]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. [2021]