Cemiplimab + Surgery for Advanced Skin Cancer

Recruiting at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic antibiotics, Antivirals

Disqualifiers: Autoimmune disease, Organ transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12-18 weeks

420 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of adding cemiplimab to standard therapy (surgery with or without radiation) versus standard therapy alone in treating patients with stage III/IV squamous cell skin cancer that is able to be removed by surgery (resectable) and that may have come back after a period of improvement (recurrent). The usual treatment for patients with resectable squamous cell skin cancer is the removal of the cancerous tissue (surgery) with or without radiation, which uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cemiplimab has been approved for the treatment of skin cancer that has spread or that cannot be removed by surgery, but it has not been approved for the treatment of skin cancer than can be removed by surgery. Adding cemiplimab to the usual treatment of surgery with or without radiation may be more effective in treating patients with stage III/IV resectable squamous cell skin cancer than the usual treatment alone.

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 medications for an active infection or certain autoimmune diseases, you may not be eligible to participate.

What data supports the effectiveness of the drug cemiplimab for advanced skin cancer?

Research shows that cemiplimab, when used before surgery, led to complete responses in 51% of patients with advanced skin cancer. It also improved survival rates compared to other treatments, making it a promising option for patients with advanced cutaneous squamous cell carcinoma. ^{1 2 3 4 5}

Is cemiplimab safe for use in humans?

Cemiplimab has been shown to be generally safe and well-tolerated in most patients with advanced cutaneous squamous cell carcinoma, with common side effects including fatigue, diarrhea, itching, and rash. Severe side effects, which are less common, can include inflammation of the lungs, heart, muscles, and liver, and the risk of treatment-related death is about 3% in clinical trials. ^{4 5 6 7 8}

How does the drug cemiplimab differ from other treatments for advanced skin cancer?

Cemiplimab is unique because it is a monoclonal antibody that targets the PD-1/PD-L1 pathway, which helps the immune system attack cancer cells. It is specifically approved for advanced cutaneous squamous cell carcinoma when surgery or radiation isn't an option, and it has shown better survival rates compared to other systemic treatments like EGFR inhibitors and chemotherapy. ^{2 4 5 6 8}

Research Team

Neil D Gross

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with stage III/IV resectable squamous cell skin cancer, either previously untreated or recurrent. Eligible participants must have a confirmed diagnosis of invasive cutaneous squamous cell carcinoma (CSCC) or related metastasis and be able to undergo surgery with curative intent. Mucosal SCC and tumors that are not resectable or involve the skull base are excluded.

Inclusion Criteria

I do not have squamous cell carcinoma in mucosal areas.

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

My skin cancer is confirmed to be squamous cell carcinoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cemiplimab intravenously every 21 days for up to 4 cycles, followed by response-adaptive surgery and optional radiation therapy

12-18 weeks

4 visits (in-person) for cemiplimab, surgery visit, and potential radiation visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Follow-up visits at 1, 6, and 12 months post-surgery, then every 3 months for 2 years, every 6 months in year 3, and annually thereafter

Treatment Details

Interventions

• Cemiplimab
• Surgical Procedure

Trial Overview The study is evaluating if adding Cemiplimab, an immunotherapy drug, to standard treatment (surgery with/without radiation) improves outcomes in treating advanced skin cancer compared to standard treatment alone. The focus is on whether this combination can better help the immune system attack the cancer.

Participant Groups

Group I: Arm 2 (cemiplimab, surgery, radiation) Experimental Treatment 9 Interventions

Patients receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo response-adaptive surgery 21 days after last dose of cemiplimab. Starting within 84 days of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Starting within 6 weeks of completion of surgery or radiation therapy (if indicated), patients without pCR receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET/CT on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

Group II: Arm 1 (surgery, radiation) Active Control 8 Interventions

Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 84 days of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo CT, MRI, and/or PET/CT on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 79 patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab treatment resulted in a high 12-month event-free survival rate of 89% and a disease-free survival rate of 92%, indicating its efficacy as a pre-surgical treatment option.

The treatment was generally safe, with only 25% of patients receiving adjuvant cemiplimab experiencing grade 3 adverse events, and no grade 4 adverse events or treatment-related deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study. Gross, ND., Miller, DM., Khushalani, NI., et al.[2023]

Cemiplimab, a PD-1 inhibitor, shows significant improvements in overall survival (OS) and progression-free survival (PFS) compared to EGFR inhibitors and pembrolizumab, with hazard ratios indicating a strong benefit.

In comparison to platinum-based chemotherapy, cemiplimab also demonstrated superior efficacy in improving overall survival for patients with advanced cutaneous squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. Keeping, S., Xu, Y., Chen, CI., et al.[2021]

Cemiplimab demonstrated a significant objective response rate of 46.1% in patients with advanced cutaneous squamous cell carcinoma (CSCC), with complete response rates of 20.3% for metastatic CSCC and 12.8% for locally advanced CSCC, indicating its efficacy as a treatment option.

Patients experienced durable improvements in quality of life and pain control, with significant enhancements observed as early as the second treatment cycle, highlighting the treatment's positive impact on overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. Rischin, D., Khushalani, NI., Schmults, CD., et al.[2022]

Cemiplimab demonstrated significant antitumor activity in patients with locally advanced cutaneous squamous cell carcinoma, with 44% of the 78 patients showing an objective response, including 13% achieving a complete response.

The treatment had an acceptable safety profile, with 44% of patients experiencing grade 3-4 adverse events, the most common being hypertension and pneumonia, and one treatment-related death due to aspiration pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Migden, MR., Khushalani, NI., Chang, ALS., et al.[2021]

Cemiplimab, an antibody treatment for locally advanced and metastatic cutaneous squamous cell carcinoma, shows promising efficacy with objective response rates between 32% and 77%, indicating it is a viable option for patients who cannot undergo surgery or radiation.

The treatment is generally safe and well-tolerated, with only 9.8% of patients experiencing adverse events severe enough to stop therapy, although there is a 3% risk of treatment-related death due to immune-mediated side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives. Mager, L., Gardeen, S., Carr, DR., et al.[2023]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab is effective for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), showing an overall objective response rate (ORR) of 53% in retrospective studies and 45% in prospective studies, indicating its potential as a viable treatment option.

However, the treatment is associated with significant adverse events, particularly in prospective studies, where 99% of patients experienced some form of treatment-related adverse events, highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: A comparative analysis of retrospective studies versus prospective studies. Wang, BC., Xiao, BY., Kuang, BH., et al.[2022]

In a Belgian cohort of seven kidney transplant recipients with advanced cutaneous squamous cell carcinoma (cSCC), cemiplimab treatment resulted in an overall response rate of 42.8%, indicating its potential efficacy in this high-risk population.

The treatment was associated with a low risk of graft rejection (14.3%) and minimal side effects, suggesting that cemiplimab is a well-tolerated option for KTR suffering from advanced cSCC who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab for advanced cutaneous squamous cell carcinoma in kidney transplant recipients. Van Meerhaeghe, T., Baurain, JF., Bechter, O., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives. [2023]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

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

The efficacy and safety of cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: A comparative analysis of retrospective studies versus prospective studies. [2022]

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

Cemiplimab for advanced cutaneous squamous cell carcinoma in kidney transplant recipients. [2023]