Chemo-Immunotherapy for Lung Cancer

(NEO-SURG Trial)

Overseen By Joshua Reuss, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must be taking: Platinum-doublet chemotherapy

Must not be taking: Systemic immunosuppressants

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

21 Participants Needed

Trial Summary

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 systemic immunosuppressive medication, you may need to stop it at least 2 weeks before starting the study treatment, unless it's a low-dose or specific type allowed by the trial.

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

Cemiplimab has shown significant effectiveness in treating advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression, improving overall survival and progression-free survival compared to chemotherapy. It is also approved for advanced cutaneous squamous cell carcinoma, highlighting its role in enhancing the immune system's response to tumors. ^{1 2 3 4 5}

What safety data exists for cemiplimab (Libtayo) in humans?

Cemiplimab (Libtayo) has been studied for safety in various cancers, including lung and skin cancer. Common side effects noted in trials include immune-related reactions, which are typical for this type of treatment, and efforts are ongoing to reduce these toxicities. ^{1 2 4 5 6}

How is the drug Cemiplimab different from other treatments for lung cancer?

Cemiplimab is unique because it is a PD-1 inhibitor that enhances the immune system's ability to fight cancer by blocking T-cell inactivation, and it can be used as a first-line treatment for non-small cell lung cancer (NSCLC) with high PD-L1 expression, either alone or with chemotherapy. ^{1 2 3 7 8}

What is the purpose of this trial?

The goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with contralateral mediastinal or ipsilateral supraclavicular lymph node (N3) involvement.. The main question it aims to answer is whether patients with stage 3 NSCLC with involvement of lymph nodes can undergo surgery to remove the cancer after receiving treatment with chemotherapy + immunotherapy. Participants will receive FDA-approved chemotherapy called platinum-doublet chemotherapy together with an immunotherapy drug targeting the immune marker PD-1 called cemiplimab. Patients will receive a 3 drug combination for 4 total treatments given every 3 weeks before surgery. After surgery, patients will have the option to undergo radiation therapy if it is recommended by their treatment team. After this, they will receive cemiplimab every 3 weeks for one year.

Research Team

Joshua Reuss, MD

Principal Investigator

Georgetown University

Eligibility Criteria

This trial is for individuals with stage III non-small cell lung cancer (NSCLC) that has spread to certain lymph nodes. Candidates must be eligible for surgery after receiving chemotherapy and immunotherapy. Details on specific inclusion or exclusion criteria are not provided.

Inclusion Criteria

My surgeon believes my tumor can be surgically removed with the goal of curing me.

My surgeon has cleared me for surgery without major health risks.

My lungs are strong enough for the surgery my doctor recommends.

Exclusion Criteria

I have active tuberculosis.

I have a history of uncontrolled HIV or hepatitis.

I have not had a severe infection in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive a combination of cemiplimab and platinum-doublet chemotherapy for 4 cycles, administered every 3 weeks before surgery

12 weeks

Surgical Resection

Participants undergo surgical resection to remove the cancer

Adjuvant Treatment

Participants receive cemiplimab every 3 weeks for one year after surgery

1 year

Radiation Therapy (optional)

Participants may undergo radiation therapy if recommended by their treatment team

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Cemiplimab

Trial Overview The study tests if patients can have successful surgery to remove NSCLC after treatment with platinum-doublet chemotherapy and cemiplimab, an immunotherapy drug targeting PD-1. Post-surgery, optional radiation therapy and additional cemiplimab treatments for one year are considered.

Participant Groups

Group I: Cemiplimab plus chemotherapy Experimental Treatment 1 Intervention

cemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery.

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?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

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]

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]

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]

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 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]

Immune checkpoint inhibitors, such as ipilimumab and anti-PD-1 agents like nivolumab and pembrolizumab, work by enhancing the immune system's ability to fight non-small cell lung cancer (NSCLC), differing from traditional chemotherapy that targets tumor cells directly.

Preliminary evidence indicates that these inhibitors can be effective as standalone treatments or in combination with chemotherapy, highlighting their potential in improving outcomes for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): the role of immune checkpoint inhibitors. Langer, CJ.[2020]

Immunotherapy is becoming a key part of first-line treatment for non-small cell lung cancer (NSCLC), with various phase 3 studies showing the effectiveness of drugs targeting PD-1, PD-L1, and CTLA-4, often in combination with chemotherapy.

Patients with high PD-L1 expression (≥ 50%) can be treated with single-agent Pembrolizumab or Atezolizumab, while those with lower expression have multiple treatment options, including combinations of immunotherapy and chemotherapy, highlighting the tailored approach based on tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. Nasser, NJ., Gorenberg, M., Agbarya, A.[2020]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

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]

6. United States 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. [2021]

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

Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): the role of immune checkpoint inhibitors. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. [2020]