Cemiplimab + Cetuximab for Oral Cancer

Overseen By Renata Ferrarotto, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Anti-PD1/PD-L1

Disqualifiers: Metastatic disease, Autoimmune, Transplant, 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: Unknown

Duration: 6 weeks

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining cemiplimab (an immunotherapy drug) and cetuximab (a targeted therapy) can control oral cavity squamous cell carcinoma that has recurred after treatment. Participants will receive these drugs for six weeks before undergoing surgery to remove the cancer. If the tumor responds well, participants may continue with cemiplimab for up to a year. The study seeks individuals whose oral cancer returned at least three months after completing initial treatment and who plan to have surgery to remove it. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroid therapy (more than 10 mg of prednisone per day or equivalent), you may need to stop or adjust it before starting the trial.

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

Previous studies have shown positive results for cemiplimab in treating advanced skin cancer, suggesting its potential safety for other cancer types. Research indicates that cemiplimab is generally well-tolerated, with most side effects being mild to moderate.

Cetuximab, another treatment in this trial, has already received approval for head and neck cancers, indicating it has passed safety tests for these conditions. Common side effects include a rash and low magnesium levels, which are usually manageable.

Trials are testing the combination of cemiplimab and cetuximab. Although detailed safety information for this combination remains limited, both treatments have individually been shown to be well-tolerated. This suggests the combination might also be safe for treating cancer, but further research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cemiplimab and cetuximab together for treating oral cancer because this combination targets the cancer cells in a unique way. Cemiplimab is an immunotherapy drug that empowers the immune system to better recognize and attack cancer cells, while cetuximab is a monoclonal antibody that blocks signals needed for cancer cell growth. This dual approach not only directly disrupts cancer cell activity but also boosts the body's natural defenses against the cancer, offering a potentially more effective treatment than the typical surgery and radiation options currently available.

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

Participants in this trial will receive a combination of cemiplimab and cetuximab to treat recurring oral cavity squamous cell carcinoma. Studies have shown that using these drugs together can effectively treat this condition. Research indicates that patients receiving this combination before surgery often experience significant tumor shrinkage or improvement. In earlier studies, patients treated with this combination lived for an average of about 12.1 months, suggesting that the treatment can help control the cancer. Additionally, cemiplimab has shown positive results in treating similar cancers, increasing confidence in its potential effectiveness. Overall, these findings suggest that this drug combination could be promising for managing this type of oral cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Renata Ferrararotto, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with a recurrence of oral cavity squamous cell carcinoma (OCSCC) at stages 3-5. It's designed to see if treatment before surgery can help manage the disease.

Inclusion Criteria

My disease returned 3 months after finishing treatment meant to cure it.

I am willing to have biopsies before and during treatment for study purposes.

I am willing to undergo additional surgery if needed.

Exclusion Criteria

I haven't taken corticosteroids in the last 14 days.

I have not needed treatment for an autoimmune disease in the last 5 years.

I do not have any health conditions that would make this study too risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab and cetuximab together for 6 weeks before salvage surgery

6 weeks

Surgery

Participants undergo salvage surgery after initial treatment

Post-Surgery Treatment

Based on tumor response, participants may receive cemiplimab alone for up to 1 year after surgery

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Cetuximab

Trial Overview The study tests combining two drugs, Cemiplimab and Cetuximab, given before salvage surgery in patients with recurrent OCSCC to evaluate their effectiveness in controlling the cancer.

How Is the Trial Designed?

Group I: Cemiplimab + Cetuximab Experimental Treatment 2 Interventions

Participants will receive cemiplimab and cetuximab together for 6 weeks, and then you will have salvage surgery. Based on how the tumor responds to the study therapy, you may also receive cemiplimab alone for up to 1 year after surgery.

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+

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

Published Research Related to This Trial

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

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 post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a case study of a 66-year-old man with metastatic oral cavity cancer, discontinuation of cetuximab due to intolerable side effects led to successful disease control with metronomic capecitabine.

This suggests that capecitabine may serve as a safe and effective alternative maintenance therapy for patients who cannot tolerate cetuximab after initial treatment with platinum-based chemotherapy and cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term disease control in a metastatic squamous cell carcinoma of the oral cavity treated with maintenance metronomic capecitabine. Muratori, L., La Salvia, A., Gorzegno, G., et al.[2020]

The weekly cetuximab plus paclitaxel (wCmab-PTX) regimen showed a best overall response rate of 48.4% and a disease control rate of 61.3% in patients with recurrent or metastatic oral squamous cell carcinoma (R/M OSCC), indicating its efficacy as a treatment option.

The treatment was associated with manageable adverse events, with significant side effects including leukopenia (16.1%) and acne-like rash (12.9%), suggesting that wCmab-PTX is a tolerable option for patients who have not responded to platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Study of Weekly Cetuximab Plus Paclitaxel for Recurrent or Metastatic Oral Squamous Cell Carcinoma. Naruse, T., Yanamoto, S., Otsuru, M., 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 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 32 head and neck squamous cell carcinoma (HNSCC) cell lines, researchers identified YAP1 amplification as a key factor associated with resistance to the EGFR-targeting antibody cetuximab, suggesting it could serve as a novel biomarker for treatment response.

The study demonstrated that higher levels of YAP1 not only correlated with cetuximab resistance but also that reducing YAP1 expression through RNA knockdown increased sensitivity to the drug, highlighting its potential role in guiding therapy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. Jerhammar, F., Johansson, AC., Ceder, R., et al.[2021]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

In a study of 65 patients with recurrent or metastatic oral squamous cell carcinoma, the combination of cetuximab and platinum-based chemotherapy showed a disease control rate of 67.7% and a median overall survival of 12.1 months, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with the most common severe side effects being skin rash (9.2%) and leukopenia (6.2%), and importantly, none of the adverse events were fatal, highlighting the safety of this therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma. Yanamoto, S., Umeda, M., Kioi, M., et al.[2019]

Eribulin, a microtubule inhibitor, can trigger a transition from a mesenchymal to an epithelial state (MET) in oral squamous cell carcinoma (OSCC) cells, particularly enhancing sensitivity to cetuximab, an anti-EGFR antibody.

In vitro studies on three OSCC cell lines showed that eribulin not only increased EGFR expression in resistant cells but also reversed the effects of TGF-β that promote epithelial-mesenchymal transition, suggesting that combining eribulin with cetuximab could be an effective new treatment strategy for OSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. Kitahara, H., Hirai, M., Kato, K., et al.[2018]

In a study of five Japanese patients with recurrent or metastatic head and neck cancer, biweekly administration of cetuximab (500 mg/m2) was found to be well tolerated, with no severe toxicities (grade 3 or higher) reported.

The main adverse effects observed were mild (grade 2) skin-related issues, indicating that biweekly cetuximab may be a safe alternative for patients who have difficulty with weekly treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly administration of cetuximab in Japanese patients with recurrent or metastatic head and neck cancer. Tanaka, N., Enokida, T., Fujisawa, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04722523

NCT04722523 | A Study of Cemiplimab With ... The purpose of this study is to find out whether combining the standard chemotherapy for head and neck cancer with the immunotherapy drugs cetuximab and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06448026

Cemiplimab and Cetuximab Prior Salvage Surgery in ... Primary Objective: - To assess the efficacy of cemiplimab and cetuximab in patients with recurrent oral cavity squamous cell carcinoma. Secondary Objective:.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18117

Neoadjuvant cemiplimab with platinum-doublet ... The primary endpoint was pathologic response rate and secondary endpoints were EFS and OS. Results: 30 patients (26 oral cavity) completed ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11693926/

Neoadjuvant Cetuximab Leading to a Complete Pathologic ... Cemiplimab has generally shown favorable outcomes in the neoadjuvant setting for advanced cutaneous squamous cell carcinoma (cSCC) [2].

5. withpower.com withpower.com/trial/phase-2-recurrence-10-2024-76647

Cemiplimab + Cetuximab for Oral Cancer What data supports the effectiveness of the drug combination Cemiplimab and Cetuximab for oral cancer? ... survival of 12.1 months, indicating its efficacy ...

6. nature.com nature.com/articles/s41467-025-59004-w

Efficacy, safety and single-cell analysis of neoadjuvant ... Efficacy, safety and single-cell analysis of neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma: a phase II trial.

7. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only

Libtayo® (cemiplimab-rwlc) Approved in the U.S. as First ... Approval based on pivotal Phase 3 C-POST trial showing Libtayo significantly reduced the risk of disease recurrence or death by 68% compared ...