Cemiplimab + Chemotherapy for Head and Neck Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marcelo Bonomi

Must not be taking: Corticosteroids, Immunosuppressants, PI3K inhibitors

Disqualifiers: Nasopharyngeal carcinoma, Brain metastases, HIV, 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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating head and neck cancer that has returned or spread. The study tests a combination of cemiplimab, an immunotherapy that may help the immune system fight cancer, with two chemotherapy drugs, paclitaxel and carboplatin, to determine their combined effectiveness. It targets individuals with squamous cell carcinoma in areas such as the mouth or throat who have not received systemic treatment for their recurrent or metastatic cancer. Participants must have completed any prior radiation or surgery at least four weeks before joining. 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 cancer research.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive treatments, you may not be eligible to participate.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive treatments, you may not be eligible to participate.

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

A previous study found cemiplimab to be well-tolerated, even by older patients with serious health issues. More than half of these patients responded positively to the treatment. Research on paclitaxel and carboplatin, especially when used together, has shown they are generally safe for patients with head and neck cancer. Weekly administration of these drugs caused fewer severe side effects than larger doses every three weeks.

Overall, cemiplimab, paclitaxel, and carboplatin have been studied separately and have demonstrated good safety records. This suggests they are generally safe for treating cancer. However, like any treatment, side effects can occur. Always discuss potential risks with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cemiplimab with chemotherapy for head and neck cancer because it offers a new way to enhance the immune system’s ability to fight cancer. Cemiplimab is a type of immunotherapy called a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells more effectively. This is different from the standard treatments, like surgery, radiation, and conventional chemotherapy alone, which directly target and kill cancer cells but may not engage the immune system as effectively. By combining cemiplimab with chemotherapy agents like carboplatin and paclitaxel, there's potential to not only shrink tumors more efficiently but also sustain the immune response against cancer longer, making it a promising option for patients.

What evidence suggests that cemiplimab combined with chemotherapy could be effective for head and neck cancer?

Research has shown that cemiplimab, when used alone, can reduce the risk of cancer recurrence or death by 68% in certain types of cancer. In real-world use, it has successfully shrunk tumors in 52% of patients, indicating effectiveness in more than half of those treated. This trial will administer a combination treatment of cemiplimab, paclitaxel, and carboplatin. Paclitaxel has demonstrated a 54.2% success rate in treating head and neck cancer when used with other treatments. When combined with carboplatin, paclitaxel has a 39% success rate, with some patients experiencing complete tumor disappearance. These findings suggest that using cemiplimab with paclitaxel and carboplatin could be a promising treatment for recurring or spreading squamous cell carcinoma of the head and neck. ^{1 4 6 7 8}

Who Is on the Research Team?

Marcelo R Bonomi, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic squamous cell carcinoma of the head and neck, who haven't had systemic therapy for this condition before. Participants must have proper kidney function, no recent vaccines, not be on immunosuppressants, and agree to use contraception. Excluded are those with certain heart conditions, active infections like HIV or hepatitis B/C, known brain metastases unless stable, or a history of pneumonitis.

Inclusion Criteria

Ability and willingness to provide written informed consent and to comply with the study visits and assessment schedule

I am fully active or can carry out light work.

Your creatinine level in the blood is less than or equal to 1.6 milligrams per deciliter.

Exclusion Criteria

Any other condition or circumstance that could interfere with adherence to the study's procedures or requirements or otherwise compromise the study's objectives in the opinion of the Principal Investigator

I do not have HIV, hepatitis B, or hepatitis C.

I have not received any live vaccines in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

A safety run-in phase of ten patients will be performed initially to assess toxicity/tolerance to the treatment combination

Up to 6 weeks

Treatment

Patients receive cemiplimab every 3 weeks for up to 104 weeks, and paclitaxel and carboplatin weekly for up to 24 weeks

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cemiplimab
• Paclitaxel

Trial Overview The trial is testing cemiplimab (an immune system-boosting monoclonal antibody) combined with low-dose paclitaxel and carboplatin (chemotherapy drugs). The goal is to see if this combination is more effective in stopping cancer growth compared to other treatments for head and neck cancers that have spread or returned after treatment.

How Is the Trial Designed?

Group I: Treatment (cemiplimab, paclitaxel, carboplatin) Experimental Treatment 3 Interventions

Patients will be treated with a combination of cemiplimab 350 mg every three weeks, with weekly combination of paclitaxel 25 mg/m2 and carboplatin AUC 1. Treatment will continue for a total of 24 months or until disease progression or unacceptable toxicity. Weekly chemotherapy will stop after six months of treatment (24 weeks). A ten patient safety run-in phase will be initially performed.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Marcelo Bonomi

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a case series of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), a combination treatment of paclitaxel, carboplatin, cetuximab, and pembrolizumab resulted in significant clinical responses, with all patients achieving an objective response (6 complete responses and 2 partial responses).

The treatment was generally safe, with manageable adverse events, although one patient experienced liver toxicity related to the immune checkpoint inhibitor. This suggests that the quadruple therapy could be a promising option for R/M HNSCC, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Response Rate to Carboplatin-Paclitaxel-Cetuximab and Pembrolizumab in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Chauffert, B., Zhou, Y., Medjkoune, L., et al.[2023]

Higher T and N stages in head and neck cancer are associated with lower rates of complete local control and survival, highlighting the need for improved treatment strategies.

Combined-modality treatments, such as induction chemotherapy followed by radiotherapy, show promise in enhancing survival and preserving organ function compared to aggressive surgery or radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modalities in the treatment of head and neck cancers. Aisner, J., Hiponia, D., Conley, B., et al.[2015]

Cytotoxic chemotherapy for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) primarily includes platinum agents, taxanes, and antimetabolic agents, which are commonly used to manage the disease.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, shows modest effectiveness in treating R/M HNSCC, highlighting the importance of a multidisciplinary approach in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. Fury, MG., Pfister, DG.[2019]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a phase 1b trial involving 20 patients with untreated recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of carboplatin, cetuximab, and everolimus showed an objective response rate of 61.5%, indicating promising efficacy.

The maximum tolerated dose of everolimus was determined to be 2.5 mg every other day, with progression-free survival averaging 8.15 months, suggesting that this treatment regimen may be effective for certain patients despite some dose-limiting toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck. Saba, NF., Hurwitz, SJ., Magliocca, K., et al.[2021]

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

In a study involving 300 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of cetuximab and cisplatin was found to be equally effective as adding paclitaxel, with median progression-free survival of 5 months for the two-drug regimen and 8 months for the three-drug regimen, but no significant difference in overall survival or objective response rates.

The results suggest that the simpler two-drug regimen of cetuximab and cisplatin could be a viable first-line treatment option, as it did not compromise patient outcomes compared to the more complex three-drug combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial. Zheng, Y., Dou, H., Li, Q., et al.[2023]

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]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

In a study of 59 patients with recurrent or metastatic head and neck cancer treated with weekly cetuximab and paclitaxel, the median progression-free survival was 5.7 months and the median overall survival was 11.8 months, indicating a potential benefit of this treatment regimen.

Patients who had previously received cetuximab experienced shorter progression-free and overall survival, suggesting that prior treatment may negatively impact the effectiveness of the Cmab-PTX combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly Cetuximab and Paclitaxel for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Fushimi, C., Baba, D., Masubuchi, T., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... Forty of 50 assessable patients (80%) had an objective response, with a complete response rate of 52%. With a median follow-up of 69 months for surviving ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41203-9/fulltext

Long-term outcomes with concurrent carboplatin, paclitaxel ... Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00176267

Paclitaxel, Carboplatin And Low Dose Radiation As ... This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery ...

5. spandidos-publications.com spandidos-publications.com/10.3892/mco.2021.2403

Weekly vs. 3‑weekly paclitaxel, carboplatin, and cetuximab ... Overall response rates were 44.4% with a median PFS of 6.2 months and a median OS of 14 months. Although these results were promising, in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10546034/

Locally advanced head and neck squamous cell ... The ≥3 AEs of IC (docetaxel + cisplatin+5-Fluorouracil) combined with CCRT (docetaxel/carboplatin + RT) was significantly higher than that of ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02625

Pembrolizumab Plus Carboplatin and Paclitaxel as First- ... Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05294900

Study Details | NCT05294900 | Trial of Neoadjuvant ... Objective: Primary objective: To evaluate the major pathologic response (mPR) of locally advanced head and neck cancer after paclitaxel and ...