Cemiplimab + Cetuximab for Oral Cancer

Overseen By Luana Guimaraes De Sousa, 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

Trial Summary

What is the purpose of this trial?

To learn if giving cemiplimab and cetuximab before salvage surgery can help to control recurrent oral cavity squamous cell carcinoma.

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.

What data supports the effectiveness of the drug combination Cemiplimab and Cetuximab for oral cancer?

Cemiplimab has been effective in treating advanced cutaneous squamous cell carcinoma by enhancing the immune system's response to tumors. Cetuximab, when combined with other treatments, has shown promise in treating oral squamous cell carcinoma by targeting specific cancer cell pathways. ^{1 2 3 4 5}

Is the combination of Cemiplimab and Cetuximab safe for humans?

Cemiplimab has been shown to have an acceptable safety profile in clinical trials for advanced cutaneous squamous cell carcinoma, with most side effects being manageable. Cetuximab has been used safely in patients with metastatic colorectal cancer, as confirmed by post-marketing surveillance in Japan. ^{1 6 7 8 9}

What makes the drug combination of Cemiplimab and Cetuximab unique for treating oral cancer?

The combination of Cemiplimab and Cetuximab is unique because it targets the epidermal growth factor receptor (EGFR), which is important in the growth of many cancers, and may offer a novel approach for oral cancer treatment by potentially overcoming resistance seen with Cetuximab alone. ^{2 5 10 11 12}

Research Team

Luana Guimaraes de Sousa, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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 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]

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 (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 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]

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]

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]

References

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

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. [2018]

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

YAP1 is a potential biomarker for cetuximab resistance in head and neck cancer. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Study of Weekly Cetuximab Plus Paclitaxel for Recurrent or Metastatic Oral Squamous Cell Carcinoma. [2021]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

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

Cemiplimab: First Global Approval. [2023]

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

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

Biweekly administration of cetuximab in Japanese patients with recurrent or metastatic head and neck cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Long-term disease control in a metastatic squamous cell carcinoma of the oral cavity treated with maintenance metronomic capecitabine. [2020]