Cemiplimab for Head and Neck Cancer

Overseen By Neil D Gross, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer therapy, Bisphosphonates, Immunosuppressants, others

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cemiplimab, an immunotherapy treatment, to evaluate its effectiveness before surgery for patients with operable head and neck cutaneous squamous cell cancer. Cemiplimab, a monoclonal antibody, aids the immune system in targeting and attacking cancer cells. The study includes patients with stage II-IV cancer that has recurred after treatment and who plan to undergo surgery. Participants must have a biopsy-confirmed diagnosis and a treatment plan involving surgery, with or without radiation. As a Phase 2 trial, this research measures cemiplimab's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant advancements in cancer treatment.

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, certain treatments like systemic immunosuppressive medications and investigational agents must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that cemiplimab is likely to be safe for humans?

Research has shown that cemiplimab is generally well-tolerated. Studies on patients with advanced cutaneous squamous cell carcinoma, a type of skin cancer, indicate that many respond well to the treatment. In one study, cemiplimab caused visible signs of cancer shrinking or disappearing in 44% to 50% of patients.

Side effects are common but usually manageable. The most reported issues include tiredness, diarrhea, itching, and nausea, affecting about 27% to 42% of patients. Importantly, these side effects were not severe enough to stop most people from continuing treatment.

Overall, cemiplimab has shown promise in clinical studies, and its tolerability makes it a potential option for those considering participation in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cemiplimab is unique because it targets the PD-1 pathway, which is a different approach compared to traditional chemotherapy or radiation treatments for head and neck cancer. This immunotherapy works by unleashing the immune system to recognize and attack cancer cells, potentially leading to better outcomes with fewer side effects. Researchers are excited about cemiplimab because it can be administered intravenously in short 30-minute sessions every three weeks, offering a more convenient option for patients.

What evidence suggests that cemiplimab might be an effective treatment for head and neck cancer?

Research has shown that cemiplimab, a type of immunotherapy, yields promising results in treating head and neck skin cancer. One study found that cemiplimab reduced the risk of cancer recurrence or death by 68%, highlighting its potential effectiveness. Cemiplimab aids the body's immune system in identifying and attacking cancer cells, thereby slowing or stopping their growth. Patients tolerated it well, with more than half responding positively to the treatment. This evidence supports cemiplimab as a potentially effective option for treating this cancer. Participants in this trial will receive cemiplimab, with or without radiation therapy, based on the treating physician's discretion. ^{1 2 3 6 7}

Who Is on the Research Team?

Neil D. Gross

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent, surgically removable stage II-IV head and neck cutaneous squamous cell cancer are eligible for this trial. They must have acceptable organ function, no severe unresolved side effects from previous cancer treatments (except hair loss), and not be pregnant or breastfeeding. Participants should not have a history of certain diseases or conditions that could interfere with the study, including autoimmune diseases, serious infections, or recent receipt of live vaccines.

Inclusion Criteria

Signed informed consent form (ICF)

Absolute neutrophil count (ANC) >= 1500 cells/uL (obtained within 4 weeks [+/-3 days] prior to study entry)

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a history of certain infections.

I have a history of certain types of cancer.

I am taking bisphosphonates for high calcium levels due to cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab intravenously every 3 weeks for up to 6 weeks, with or without radiation therapy

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Periodic visits

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab

Trial Overview The trial is testing Cemiplimab's effectiveness when given before surgery to patients with specific types of skin cancer on the head and neck. Cemiplimab is an immunotherapy drug designed to boost the body's immune response against cancer cells by blocking a pathway tumors use to evade attack.

How Is the Trial Designed?

Group I: Treatment (cemiplimab) Experimental Treatment 1 Intervention

Patients receive cemiplimab IV over 30 minutes every 3 weeks. Cycles repeat every 3 weeks for up to 6 weeks with or without radiation therapy at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cetuximab, an anti-EGFR monoclonal antibody, significantly enhances the effectiveness of radiotherapy in treating squamous cell carcinoma of the head and neck, leading to better locoregional control and improved survival rates compared to radiotherapy alone.

Despite its benefits, only a small percentage of patients respond to anti-EGFR therapies, highlighting the need for further research into the mechanisms of treatment resistance and the development of predictive biomarkers to identify which patients are most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal Growth Factor Receptor Inhibition in Squamous Cell Carcinoma of the Head and Neck. Machiels, JP., Schmitz, S.[2019]

In the CheckMate 141 trial involving 361 patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck, nivolumab significantly improved patient-reported outcomes (PROs) compared to standard therapies, with no clinically meaningful deterioration in quality of life for nivolumab patients.

Nivolumab not only stabilized symptoms and functioning but also delayed the time to deterioration in quality of life measures, making it a promising new standard-of-care treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Harrington, KJ., Ferris, RL., Blumenschein, G., et al.[2022]

Cemiplimab combined with radiation therapy, cyclophosphamide, and GM-CSF did not show improved efficacy compared to standard PD-1 inhibitor monotherapy in treating refractory and metastatic head and neck squamous cell carcinoma, based on a study of 15 patients.

The safety profile of the combination therapy was consistent with previous findings for cemiplimab alone, with no new safety concerns identified, although common side effects included fatigue and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Babiker, H., Brana, I., Mahadevan, D., et al.[2021]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

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 small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

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]

Patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, but new treatments targeting specific pathways are emerging.

Cetuximab, pembrolizumab, and nivolumab are FDA-approved therapies that target the epidermal growth factor receptor and PD-1, respectively, showing promise in improving treatment outcomes for R/M HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies. Moreira, J., Tobias, A., O'Brien, MP., et al.[2022]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study of 46 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of weekly paclitaxel and cetuximab showed a promising overall response rate of 54%, with 22% achieving complete responses.

The treatment was well tolerated, with a disease control rate of 80% and median overall survival of 8.1 months, making it a potential option for patients who cannot receive platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Hitt, R., Irigoyen, A., Cortes-Funes, H., et al.[2022]

In a phase 1b trial involving 20 patients with untreated recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of carboplatin, cetuximab, and everolimus showed an objective response rate of 61.5%, indicating promising efficacy.

The maximum tolerated dose of everolimus was determined to be 2.5 mg every other day, with progression-free survival averaging 8.15 months, suggesting that this treatment regimen may be effective for certain patients despite some dose-limiting toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck. Saba, NF., Hurwitz, SJ., Magliocca, K., et al.[2021]

Citations

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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).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6001

Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo ... Cemiplimab is the first systemic therapy to demonstrate a statistically significant and clinically meaningful reduction in disease recurrence as adjuvant ...

3. 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 with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772611823000071

Real-world data on tolerability and clinical response of ... Cemiplimab demonstrated to be well-tolerated, even in elderly patients with severe comorbidities, achieving an objective response in 52% of patients.

5. nejm.org nejm.org/doi/pdf/10.1056/NEJMoa2502449

Adjuvant Cemiplimab or Placebo in High The current trial was successful in defining a popu- lation of patients at high risk for recurrence of cutaneous squamous-cell carcinoma as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9844515/

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous ... In studies involving patients with advanced cutaneous squamous-cell carcinoma, cemiplimab was associated with an objective response in 44 to 50% of patients, ...

7. news.sanofi.us news.sanofi.us/2019-05-16-Updated-Libtayo-R-cemiplimab-rwlc-Results-Reinforce-Durable-and-Substantial-Response-Rates-in-Advanced-Cutaneous-Squamous-Cell-Carcinoma

Updated Libtayo® (cemiplimab-rwlc) Results Reinforce ... Among patients with locally advanced CSCC, the most common adverse events (AEs) were fatigue (42%), diarrhea and pruritus (both 27%) and nausea ...