Radioimmunotherapy vs Chemoimmunotherapy for Non-Small Cell Lung Cancer

Overseen By Julia Muuse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Uncontrolled illness, HIV, 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

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

Compensation: Varies

Number of Visits: 13

112 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if Cemiplimab with chemotherapy or Cemiplimab with stereotactic body radiation therapy (SBRT) works as treatment for stages IB, II, and III (N2) Non-Small Cell Lung Cancer (NSCLC). Before surgery to remove their lung cancer, participants will take: 1. Cemiplimab with chemotherapy (Arm A) every 3 weeks for up to 3 doses, OR 2. Cemiplimab every 3 weeks for up to 3 doses with SBRT (Arm B). SBRT will be given on day 1 before taking cemiplimab, then SBRT alone on day 2 and day 3. Four to 12 weeks following surgery, participants in both Arm A and Arm B will receive treatment with cemiplimab for one year.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial, except for certain types like inhaled or topical steroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug cemiplimab for treating non-small cell lung cancer?

Research shows that cemiplimab, when used as a first-line treatment for advanced non-small cell lung cancer with high PD-L1 expression (at least 50%), provides significant survival benefits. This is supported by a 35-month follow-up study indicating improved outcomes when cemiplimab is used alone or with chemotherapy. ^{1 2 3 4 5}

Is cemiplimab safe for humans?

Cemiplimab has been studied in various cancers, including non-small cell lung cancer and cervical cancer, and is generally considered safe, though it can cause side effects like immune-related reactions. In clinical trials, some patients experienced serious side effects, but these were manageable with medical care. ^{1 2 6 7 8}

How is the treatment Cemiplimab different from other treatments for non-small cell lung cancer?

Cemiplimab, when combined with radiation therapy, may enhance the body's immune response against cancer cells, potentially improving survival rates compared to using immunotherapy or chemotherapy alone. This combination, known as radioimmunotherapy, is unique because it not only targets the tumor directly but also stimulates the immune system to attack cancer cells throughout the body. ^{9 10 11 12 13}

Research Team

Nasser K Altorki, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for individuals with stages IB, II, and III (N2) Non-Small Cell Lung Cancer who are planning to have surgery. Participants must be fit for both chemotherapy and immunotherapy. They cannot join if they've had previous treatments for NSCLC or have certain medical conditions that the study outlines.

Inclusion Criteria

Measurable disease, as defined by RECIST v1.1.

WOCBP must have a negative serum (beta-hCG) at screening.

WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment.

Exclusion Criteria

I do not have HIV, hepatitis B, or hepatitis C.

I have a lung condition treated with high-dose steroids.

I have had a stem cell or organ transplant in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive Cemiplimab with chemotherapy or Cemiplimab with SBRT before surgery

9-13 weeks

Every 3 weeks for up to 3 doses

Surgery

Surgical resection of lung cancer

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive Cemiplimab post-surgery for one year

1 year

Every 3 weeks for 4 treatments, then every 6 weeks for 11 treatments

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months for 3 years, then yearly for years 4-5

Treatment Details

Interventions

• Cemiplimab
• Platinum-based Chemotherapy
• Stereotactic Body Radiation Therapy

Trial Overview The trial tests two pre-surgery treatments: Cemiplimab combined with platinum-based chemotherapy (Arm A), or Cemiplimab with stereotactic body radiation therapy (SBRT) (Arm B). After surgery, participants in both groups will continue to receive Cemiplimab for one year.

Participant Groups

Group I: Cemiplimab with chemotherapy (Arm A) Experimental Treatment 2 Interventions

Before lung cancer surgery: 1. Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles. 2. Platinum-based chemotherapy intravenously every 3 weeks up to 3 cycles. After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).

Group II: Cemiplimab with SBRT (Arm B) Experimental Treatment 2 Interventions

Before lung cancer surgery: 1. Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles. 2. SBRT on days 1, 2, and 3. After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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, 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]

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]

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]

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]

The updated population pharmacokinetic model for cemiplimab, based on data from 1062 patients, demonstrated improved stability and robustness, successfully validating its pharmacokinetics in patients with recurrent or metastatic cervical cancer.

Despite the improved model, the analysis revealed no significant exposure-response relationships for efficacy (overall survival, progression-free survival, duration of response, objective response rate) or safety (immune-related adverse events), indicating that higher drug exposure did not correlate with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer. Nguyen, JH., Epling, D., Dolphin, N., et al.[2023]

In a subanalysis of the KEYNOTE-024 study involving 40 Japanese patients with untreated metastatic non-small-cell lung cancer, pembrolizumab significantly improved progression-free survival (HR 0.25) and overall survival (HR 0.39) compared to chemotherapy.

Both treatment groups experienced high rates of treatment-related adverse events (100% for pembrolizumab and 95% for chemotherapy), but the safety profile was manageable, with a notable occurrence of immune-mediated adverse events in 52% of pembrolizumab patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset. Satouchi, M., Nosaki, K., Takahashi, T., et al.[2021]

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 study of 44,498 patients with stage IV non-small-cell lung cancer (NSCLC), stereotactic radiotherapy (SRT) was associated with improved overall survival (OS), showing a hazard ratio of 0.78, indicating a significant benefit regardless of the type of systemic treatment used.

The combination of SRT and immunotherapy showed promising results, with patients receiving SRT having a median OS of 18.2 months compared to 14.3 months for those on chemotherapy, suggesting that SRT may enhance the effectiveness of immunotherapy and warrants further investigation in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer: a National Cancer Database analysis. Foster, CC., Sher, DJ., Rusthoven, CG., et al.[2020]

Recent advancements in radiotherapy for lung cancer include various administration methods, such as hyperfractionated and accelerated radiotherapy, which aim to improve treatment efficacy while minimizing damage to healthy tissues.

The use of radiosensitizing agents, like 5-fluorouracil and platinum salts, alongside radiotherapy has shown promise in enhancing treatment outcomes for both non-small-cell and small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New administration modalities for radiotherapy in lung cancer]. Touboul, E., Deniaud-Alexandre, E., Pereira, R., et al.[2018]

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]

Immunotherapy and targeted biologics have significantly improved survival rates for patients with non-small cell lung cancer (NSCLC), especially when combined with standard treatments like surgery and radiotherapy.

Radiotherapy not only enhances the effectiveness of immunotherapy on treated tumors but can also trigger immune responses in untreated distant tumors, suggesting a synergistic approach to treating both early-stage and metastatic NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer-A Stimulating Partnership. Dams, RV., Yuan, Y., Robinson, CG., et al.[2021]

Immune checkpoint inhibitors have significantly improved survival rates in many patients with non-small cell lung cancer (NSCLC) and generally have a good safety profile, but not all patients respond positively to these treatments.

Combination strategies involving chemotherapy or radiotherapy with immunotherapy are being explored to enhance treatment efficacy, as some patients may experience accelerated tumor progression with PD-1 or PD-L1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer? Lazzari, C., Karachaliou, N., Bulotta, A., et al.[2022]

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. 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]

3. 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]

4. England 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. [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. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer. [2023]

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

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset. [2021]

8. England pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer: a National Cancer Database analysis. [2020]

10. France pubmed.ncbi.nlm.nih.gov

[New administration modalities for radiotherapy in lung cancer]. [2018]

11. Japan pubmed.ncbi.nlm.nih.gov

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

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

Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer-A Stimulating Partnership. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer? [2022]