Pembrolizumab + Cetuximab for Head and Neck Cancer

Recruiting at 3 trial locations

Overseen By Gerald Henderson, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: Active infection, Autoimmune 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: 3

Duration: 6 months

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab and cetuximab, for patients with head and neck cancer that has returned or spread. Pembrolizumab helps the immune system fight cancer, and cetuximab attacks the cancer cells directly. Both drugs are used in treating head and neck squamous cell carcinoma.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have received chemotherapy, radiotherapy, or certain other treatments within 4 weeks before the trial starts.

Is the combination of Pembrolizumab and Cetuximab safe for humans?

Cetuximab is generally considered safe and well-tolerated, with common mild skin-related side effects. However, it can cause rare but serious side effects like persistent corneal erosion (eye surface damage). ^{1 2 3 4 5}

How is the drug combination of pembrolizumab and cetuximab unique for head and neck cancer?

The combination of pembrolizumab and cetuximab is unique for head and neck cancer because it targets different pathways in cancer cells, potentially offering a new option for patients who are resistant to standard treatments like cisplatin. This combination may be particularly beneficial for those with recurrent or metastatic cancer and other health issues, such as kidney problems. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination Pembrolizumab and Cetuximab for head and neck cancer?

Cetuximab, when used with other treatments like chemotherapy, has shown effectiveness in improving response rates in head and neck cancer. Pembrolizumab and Cetuximab together may be beneficial, especially in cases where other treatments have failed, although more research is needed to confirm their combined effectiveness. ^{1 6 10 11 12}

Who Is on the Research Team?

Assuntina Sacco, M.D.

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) that can't be treated with surgery or radiation. Participants must have good organ function, performance status of 0 or 1, and not be pregnant or planning to become pregnant. They should agree to use contraception and have not received certain treatments before the study.

Inclusion Criteria

I am a woman able to have children and have a recent negative pregnancy test.

I am fully active or can carry out light work.

Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

I have not had major surgery or fully recovered from surgery within the last 14 days.

Patient is currently receiving or has received another investigational agent within 4 weeks prior to Day 1 of study

I have an autoimmune disease treated with medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive pembrolizumab and cetuximab. Pembrolizumab is administered every 3 weeks and cetuximab is administered weekly.

6 months

Pembrolizumab: every 3 weeks; Cetuximab: weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Pembrolizumab

Trial Overview The trial tests a combination therapy using Pembrolizumab and Cetuximab in four different patient groups based on their previous treatments. It's an open-label phase II study across multiple centers aiming to enroll a total of 83 patients who will receive this combined treatment.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 1 Intervention

cutaneous HNSCC Pembrolizumab (Keytruda®): Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks. Cetuximab (Erbitux®): The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

Group II: Cohort 3 Experimental Treatment 1 Intervention

PD-1/PD-L1 inhibitor-refractory, cetuximab-refractory Pembrolizumab (Keytruda®): Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks. Cetuximab (Erbitux®): The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

Group III: Cohort 2 Experimental Treatment 1 Intervention

PD-1/PD-L1 inhibitor-refractory, cetuximab-naïve Pembrolizumab (Keytruda®): Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks. Cetuximab (Erbitux®): The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

Group IV: Cohort 1 Experimental Treatment 1 Intervention

PD-1/PD-L1 inhibitor-naïve, cetuximab-naïve Pembrolizumab (Keytruda®): Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks. Cetuximab (Erbitux®): The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Assuntina G. Sacco, MD

Lead Sponsor

Trials

1

Recruited

80+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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]

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]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Cetuximab is an effective treatment for squamous cell carcinoma of the head and neck, enhancing the effects of radiotherapy and improving response rates when combined with cisplatin chemotherapy, as indicated by a significant hazard ratio for progression of 0.78.

The most common side effect of cetuximab is an acneiform rash, which occurs in 70-80% of patients and may serve as a prognostic marker for treatment response and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Burtness, B.[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]

Cetuximab, an EGFR-inhibiting antibody used for treating certain cancers, is generally considered safe and well-tolerated, but this case highlights the potential for severe complications following its use, particularly in complex surgical situations.

The patient experienced a rare and fatal combination of complications after surgery, raising concerns about the safety of cetuximab in the context of surgical procedures, and emphasizing the need for careful monitoring and documentation of adverse effects in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. Knauer, M., Haid, A., Ammann, K., et al.[2021]

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, has shown repeated effectiveness in treating a patient with nonresectable squamous cell skin cancer, which is significant given the poor prognosis of advanced cases.

This case suggests that cetuximab could be a valuable treatment option for patients with squamous cell carcinomas that express the epidermal growth factor receptor, particularly in palliative care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Suen, JK., Bressler, L., Shord, SS., et al.[2022]

Cetuximab treatment in a 62-year-old patient with colorectal carcinoma led to persistent corneal erosions and accelerated eyelash growth, highlighting significant ocular side effects of this medication.

Topical application of EGF (epidermal growth factor) successfully healed the corneal erosions within 7 to 19 days, suggesting that EGF eyedrops may be an effective treatment for patients experiencing these side effects while continuing cetuximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persisting corneal erosion under cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody). Foerster, CG., Cursiefen, C., Kruse, FE.[2022]

In a study of 180 patients with head and neck cancer, those treated with cetuximab experienced significantly higher rates of acute dermal toxicity (34.5%) compared to those who did not receive cetuximab (10.3%).

Despite the increased skin toxicity, there were no significant differences in local control or overall survival between patients treated with cetuximab and those treated without it, indicating that cetuximab does not improve survival outcomes when combined with IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. Bibault, JE., Morelle, M., Perrier, L., et al.[2022]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

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]

Citations

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

Cetuximab. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the treatment of squamous cell cancer of the head and neck. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. [2022]

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

Persisting corneal erosion under cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody). [2022]

10. France pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer. [2022]

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

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

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

Is there a role for cetuximab in non small cell lung cancer? [2018]