Cemiplimab + Surgery for Advanced Skin Cancer

Recruiting at 172 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding cemiplimab, an immunotherapy drug, to the usual treatment of surgery with or without radiation can better treat advanced squamous cell skin cancer. Squamous cell skin cancer can recur after treatment. Cemiplimab may help the immune system fight cancer more effectively. The trial seeks participants with advanced squamous cell skin cancer that can be surgically removed and has not been treated with other systemic therapies. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cemiplimab is generally well-tolerated by patients. Studies have found it safe and effective for those with advanced skin cancer. Specifically, one study reported that up to 49% of patients responded positively to cemiplimab treatment.

Although cemiplimab is usually safe, some patients experienced side effects, including immune-related reactions where the immune system mistakenly attacks healthy cells. However, cemiplimab is considered safer compared to other treatments. The FDA has approved it for certain types of skin cancer, indicating its safety for human use. It is important to consult a healthcare provider about potential side effects and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for skin cancer?

Researchers are excited about cemiplimab for advanced skin cancer because it represents a novel approach compared to the standard treatments like surgery and radiation alone. Unlike traditional treatments, cemiplimab is an immunotherapy that works by blocking the PD-1 pathway, helping the immune system better recognize and attack cancer cells. Additionally, combining cemiplimab with surgery and radiation might enhance treatment effectiveness by potentially reducing tumor size before surgery and addressing any remaining cancer cells post-surgery. This multi-faceted approach could improve outcomes for patients with advanced skin cancer.

What evidence suggests that this trial's treatments could be effective for advanced skin cancer?

Research has shown that cemiplimab is effective in treating squamous cell skin cancer. Studies found that over 60% of patients with advanced cancer experienced complete remission after using cemiplimab. Specifically, one study showed that cemiplimab reduced the risk of cancer recurrence or death by 68%. Patients receiving cemiplimab had a median progression-free period of about 14.7 months. In this trial, one group of participants will receive cemiplimab combined with surgery and radiation, while another group will receive only surgery and radiation. These findings suggest that adding cemiplimab to standard treatments like surgery and radiation might be more effective for surgically removable squamous cell skin cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Neil D Gross

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 12 weeks 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 prior to treatment, and CT and/or MRI on study and 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 6-12 weeks 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 prior to treatment, 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+

Published Research Related to This Trial

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]

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, 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, 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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40075670/

Effectiveness and Toxicity of Cemiplimab Therapy for ... Conclusions: Cemiplimab produced complete remissions in over 60% of patients with locally advanced and metastatic squamous cell skin cancers, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9533

CemiplimAb-rwlc survivorship and epidemiology (CASE) Median PFS was 14.7 (95% CI: 12.5, 21.1) months, with survival at 12 months estimated at 59.5% (95% CI: 51.4, 66.7). Treatment-related irAEs ...

3. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00041-3/fulltext

Cemiplimab in locally advanced or metastatic cutaneous ... Cemiplimab proved highly effective and safe in this real-world cohort of patients with laCSCC or mCSCC, confirming its therapeutic value in the ...

4. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-phase-3-data-adjuvant-treatment-post

Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant ... Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, the primary endpoint of the trial (p<0.0001).

5. mdpi.com mdpi.com/2072-6694/17/5/823

Effectiveness and Toxicity of Cemiplimab Therapy for ... Conclusions: Cemiplimab produced complete remissions in over 60% of patients with locally advanced and metastatic squamous cell skin cancers, allowing elective ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11268751/

Real-World Treatment Patterns and Outcomes of Cemiplimab ... Most cases of CSCC are cured by surgery/radiation, but an estimated 1% to 5% of patients will develop advanced disease, which is associated ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879406821000527

Real world safety outcomes using cemiplimab for ... Anti-PD-1, such as cemiplimab, seems to harbour the best safety profile and good response rates (up to 49%) [3]. However, patients with advanced cSCC are often ...

8. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2502449

Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous ... The estimated 24-month disease-free survival was 87.1% (95% CI, 80.3 to 91.6) with cemiplimab and 64.1% (95% CI, 55.9 to 71.1) with placebo.