Pembrolizumab + Cetuximab for Head and Neck Cancer

Not currently recruiting at 4 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pembrolizumab (an immunotherapy drug) and cetuximab (a targeted therapy drug), for head and neck cancer that has returned or spread. The goal is to determine if these drugs work well together in different patient groups, including those who have never tried similar treatments and those whose cancer did not respond to previous therapies. People with head and neck cancer who cannot undergo surgery or radiation might be suitable candidates. The trial occurs at several locations, including cancer centers in California, Michigan, and Washington. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that pembrolizumab and cetuximab, when tested together, appear safe for patients with head and neck cancer. Studies indicate that most patients tolerate this combination well, experiencing only mild to moderate side effects such as tiredness, skin rashes, and nausea.

Another study found this drug combination effective and safe for treating similar conditions, with serious side effects being rare. Both pembrolizumab and cetuximab have FDA approval for other uses, indicating a known safety record.

The trial is currently in a phase focused on collecting more safety data. At this stage, the emphasis is on both the treatment's effectiveness and ensuring patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and cetuximab for head and neck cancer because these drugs work together to enhance the immune system's ability to fight cancer. Pembrolizumab is a PD-1 inhibitor, which helps the immune system detect and attack cancer cells more effectively, while cetuximab targets the epidermal growth factor receptor (EGFR) on cancer cells, disrupting their growth. Unlike standard treatments that often focus on chemotherapy or radiation, this combo offers a targeted approach that could potentially improve outcomes and reduce side effects. By combining these two mechanisms, the treatment has the potential to be more effective for patients who haven't responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will evaluate the combination of pembrolizumab and cetuximab for treating head and neck squamous cell carcinoma (HNSCC). Research shows that using pembrolizumab and cetuximab together may help treat HNSCC. In past studies, this combination effectively treated HNSCC that had returned or spread. Patients taking pembrolizumab, with or without chemotherapy, lived longer than those taking cetuximab with chemotherapy. Additionally, the combination of pembrolizumab and cetuximab demonstrated a response rate of 36-43% and average survival times of 13-15 months in similar cases. These results suggest that this combination might be useful in managing head and neck cancer, especially when the disease has returned or spread. ^{2 6 7 8 9}

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

Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

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

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 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]

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 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]

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, 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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12140401/

Pembrolizumab plus cetuximab in patients with recurrent or ... Pembrolizumab with platinum-based chemotherapy showed response rates of 36–43% and median overall survival of 13–15 months based on the results of the total ...

2. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT03082534

UCSD Head and Neck Squamous Cell Carcinoma Trial This is a prospective, multi-center, open-label, non-randomized, multi-arm phase II trial to evaluate the efficacy of combination therapy with pembrolizumab ...

3. onclive.com onclive.com/view/pembrolizumab-with-or-without-chemo-has-increased-efficacy-with-increasing-pd-l1-expression-in-hnscc

Pembrolizumab With or Without Chemo Has Increased ... Pembrolizumab with or without chemotherapy resulted in a numerically longer overall survival benefit vs cetuximab plus chemotherapy in patients with head and ...

4. jitc.bmj.com jitc.bmj.com/content/10/10/e005158

Efficacy of cetuximab plus PD-1 inhibitor differs by HPV ... We identified all related clinical trials and assessed whether the efficacy of the combination therapy was increased compared with PD-1 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204521001364

Pembrolizumab plus cetuximab in patients with recurrent or ... Pembrolizumab combined with cetuximab shows promising clinical activity for recurrent or metastatic HNSCC, and merits further investigation.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02358031

NCT02358031 | A Study of Pembrolizumab (MK-3475) for ... A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02508

Updated Results of the Phase III KEYNOTE-048 Study Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1574988/full

A retrospective efficacy and safety study of pembrolizumab ... Multiple studies have corroborated the safety and efficacy of the TP regimen combined with cetuximab (TP + CETUX) in patients with locally advanced head and ...