Cemiplimab + Cetuximab for Head and Neck Cancer

Overseen By Kara Hoffman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Autoimmune disease, Pneumonitis, HIV, Hepatitis, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: 4

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, cemiplimab (an immunotherapy drug) and cetuximab (a targeted therapy), to assess their safety and effectiveness for people with a specific type of head and neck cancer called squamous cell carcinoma. The researchers aim to determine if these drugs can benefit patients before surgery. People newly diagnosed with surgically removable head and neck squamous cell carcinoma might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found that using cemiplimab with cetuximab was safe, consistent with earlier research. No new safety issues arose when these drugs were combined. Cemiplimab helps the immune system fight cancer, while cetuximab enhances the effectiveness of standard treatments like chemotherapy. Some side effects, such as skin reactions or tiredness, can occur, but they are usually manageable. Overall, most patients handled the combination well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cemiplimab and cetuximab for head and neck cancer because it takes a unique approach by combining two powerful agents. Cemiplimab is an immunotherapy that works by unleashing the immune system to attack cancer cells, which is different from the traditional chemotherapy and radiation treatments. Cetuximab, on the other hand, targets a specific protein (EGFR) on cancer cells, helping to slow their growth. This combination aims to enhance cancer-fighting effects by both stimulating the immune response and directly inhibiting cancer cell growth. This dual action could potentially offer more effective results than current standard treatments alone.

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

This trial will investigate the combination of cemiplimab and cetuximab for treating head and neck cancer. Studies have shown that this combination can help treat this type of cancer. In one early study, 70% of patients experienced complete or partial tumor shrinkage after receiving these drugs. Another study found that this combination reduced tumor size, sometimes eliminating the need for additional radiation therapy. Overall, using cemiplimab and cetuximab together has shown promising results in effectively treating head and neck cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Christine Chung

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with head and neck squamous cell carcinoma (HNSCC) that can be surgically removed are eligible for this trial. They must have good performance status, meet lab criteria, provide tumor tissue for testing, agree to birth control if of childbearing potential, and commit to the study schedule. Excluded are those with severe allergies to similar drugs or red meat/tick bite history, HIV/Hepatitis B/C infections, certain heart conditions, active autoimmune diseases or pneumonitis.

Inclusion Criteria

Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted

Must be able and willing to comply to the study visit schedule and protocol requirements

I am fully active or have some restrictions but can still carry out light work.

Exclusion Criteria

Patient with a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or if the patient had red meat allergy/tick bite history

Patients with a known history of human immunodeficiency virus (HIV) infection

I am currently being treated for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive cemiplimab and cetuximab before surgery

4 weeks

4 visits (in-person)

Surgery

Participants undergo surgery for head and neck squamous cell carcinoma

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Cetuximab

Trial Overview The trial is testing the safety and benefits of combining two drugs—Cemiplimab and Cetuximab—before surgery in patients with HNSCC. It's a Phase II study where participants receive both medications as part of their pre-surgical treatment regimen.

How Is the Trial Designed?

Group I: Neoadjuvant Cetuximab and Cemiplimab Treatment Experimental Treatment 2 Interventions

Cemiplimab: 350 mg IV dose on C1D1 and C2D1 Cetuximab: 400mg/m2 loading dose on C1D1 followed by 250 mg/m2 IV weekly doses on C1D8, C1D15, and C2D1 (total 4 doses including the loading dose).

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Cetuximab is a monoclonal antibody that effectively inhibits the epidermal growth factor receptor (EGFR), which plays a crucial role in tumor growth and resistance to treatments like chemotherapy and radiotherapy.

Clinical data suggest that cetuximab not only has its own anticancer effects but may also enhance the effectiveness of chemotherapy and radiotherapy in patients with advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. Merlano, M., Occelli, M.[2021]

Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), shows only modest effectiveness as a standalone treatment for advanced non-small cell lung cancer (NSCLC), with limited benefits when added to chemotherapy based on phase II studies.

However, cetuximab has demonstrated improved survival rates when combined with radiotherapy in head and neck cancer, and ongoing research is exploring its potential benefits in combination with other treatments for locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for cetuximab in non small cell lung cancer? Morgensztern, D., Govindan, R.[2018]

Cetuximab is a promising treatment for patients with recurrent or metastatic squamous cell cancer of the head and neck who have not responded to cisplatin-based chemotherapy, due to its targeted mechanism and ability to work alongside existing treatments.

When used with radiotherapy for advanced cases, cetuximab does not increase the typical toxicity associated with head and neck radiation, making it a safer alternative for patients unable to tolerate standard cisplatin-based chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of EGFR-targeting strategies in the treatment of head and neck cancer. Dequanter, D., Shahla, M., Paulus, P., et al.[2021]

Cetuximab, an EGFR antagonist, enhances the effectiveness of radiotherapy in treating advanced head and neck cancer without increasing the usual toxicity associated with radiation or chemotherapy.

The presence of EGFR in nearly all head and neck carcinoma cases presents a significant therapeutic opportunity, as its expression is linked to poorer outcomes in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in squamous cell head and neck carcinomas. Gebbia, V., Giuliani, F., Valori, VM., et al.[2020]

Cetuximab, an epidermal growth factor receptor inhibitor, shows promise in treating advanced squamous cell carcinoma of the head and neck due to the common expression of this protein in tumors.

Clinical trials indicate that cetuximab has modest effectiveness when used alongside chemotherapy or radiotherapy, suggesting it can be a valuable addition to treatment regimens for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cetuximab in combination with radiotherapy or chemotherapy against advanced squamous cell carcinoma of the head and neck. Li, JZ., Zheng, JW., Zhang, ZY.[2019]

Cetuximab is a crucial treatment for head and neck cancer, significantly improving survival rates when combined with cisplatin and 5-fluorouracil in patients with recurrent or metastatic disease, as shown in the EXTREME study.

It is also effective as a standalone treatment or with radiation therapy for patients with locally advanced inoperable disease, and ongoing research is exploring its combination with other targeted therapies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent results of cetuximab use in the treatment of squamous cell carcinoma of the head and neck. Perri, F., Longo, F., Ionna, F., et al.[2021]

In a study of 167 patients with metastatic colorectal cancer and head-neck cancer, experiencing cutaneous adverse effects from cetuximab was linked to a significantly lower risk of mortality at 6 months, suggesting a potential positive association between these skin reactions and patient survival.

The analysis revealed that patients with cutaneous reactions had a relative risk of mortality of 0.34 overall, with specific risks of 0.45 for metastatic colorectal cancer and 0.25 for head-neck cancer, indicating that these reactions may serve as a marker for better outcomes in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cetuximab cutaneous adverse drug reactions: a marker of efficacy for metastatic colorectal cancer and head-neck cancer?]. Soussan-Dahan, M., Lapeyre-Mestre, M., Bondon-Guitton, E., et al.[2015]

In a Phase III trial, adding cetuximab to radiotherapy for locoregionally advanced squamous cell carcinoma of the head and neck significantly improved median locoregional control from 14.9 to 24.4 months and overall survival from 29.3 to 49.0 months.

For patients with platinum-refractory recurrent or metastatic disease, cetuximab combined with platinum/5-fluorouracil showed improved survival, response rates (10-13%), and disease control (46-56%), along with better symptom management compared to platinum/5-fluorouracil alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. Specenier, P., Vermorken, JB.[2019]

In a study of 37 patients with advanced head and neck cancer who were unsuitable for platinum-based chemotherapy, cetuximab combined with radiotherapy showed a 2-year overall survival rate of 44.4%, indicating its potential as an effective treatment option.

While 86% of patients completed their planned radiotherapy, the treatment was associated with significant skin toxicity, as 40.5% experienced severe dermatitis, highlighting the need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab with radiotherapy in patients with loco-regionally advanced squamous cell carcinoma of head and neck unsuitable or ineligible for concurrent platinum-based chemo-radiotherapy: Ready for routine clinical practice? Agarwal, JP., Gupta, T., Kalyani, N., et al.[2015]

In a study analyzing 3,086 reports of adverse events from cetuximab therapy for head and neck cancer, 89% of the events were classified as serious, with mucosal inflammation being the most common issue.

The study identified that receiving cetuximab treatment outside the US and using it alongside other medications significantly increased the risk of serious adverse outcomes, highlighting the need for careful monitoring in these situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes. Stanbouly, D., Philipone, E., Morlandt, AB., et al.[2022]

In a study of 28 patients with head and neck squamous cell carcinomas, higher plasma concentrations of cetuximab at Day 7 were associated with better tumor response and longer progression-free survival, indicating the importance of drug exposure in treatment outcomes.

Performance status (PS) significantly influenced cetuximab clearance and distribution, suggesting that patients with poorer PS may experience lower drug exposure and worse outcomes, highlighting the need for careful patient assessment in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab pharmacokinetic/pharmacodynamics relationships in advanced head and neck carcinoma patients. Le Louedec, F., Alix-Panabières, C., Lafont, T., et al.[2021]

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]

In a study involving 32 patients with advanced head and neck cancer, the addition of cetuximab to a treatment regimen of paclitaxel, carboplatin, and radiation was found to increase dermatologic toxicities, with 44% experiencing grade 3 radiation dermatitis.

Despite the increased skin toxicity, the combination treatment did not lead to higher mucosal toxicity compared to previous studies, suggesting that while cetuximab may enhance side effects, it does not worsen certain other adverse effects associated with cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. Birnbaum, A., Dipetrillo, T., Rathore, R., et al.[2015]

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]

Citations

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859P Neoadjuvant cemiplimab with platinum-doublet ... This pilot study evaluates whether the combination of neoadjuvant (NA) cemiplimab + platinum-doublet chemotherapy + cetuximab is safe, feasible, and effective ...

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Immunotherapy followed by cetuximab in locally advanced/ ... Immunotherapy with pembrolizumab and cemiplimab achieves an overall response rate (ORR) of 34–51 % in locally advanced/metastatic (LA/M) cSCC, ...

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Neoadjuvant cemiplimab with platinum-doublet ... This pilot study evaluates whether the combination of neoadjuvant cemiplimab + platinum-doublet chemotherapy + cetuximab is safe, feasible, and ...

7. withpower.com withpower.com/trial/phase-2-carcinoma-2-2025-84242

Cemiplimab + Cetuximab for Head and Neck Cancer Cemiplimab has a safety profile consistent with previous reports, showing no new safety concerns when used in combination with other treatments. Cetuximab ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6536039/

Cetuximab-Containing Combinations in Locally Advanced ... The survival benefit obtained by the addition of cetuximab to RT was confirmed by the 5-year update of the Bonner trial (5-year OS of 45.6% for ...