Cemiplimab + Chemotherapy for Head and Neck Cancer

Overseen By Li Zichen,

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Krzysztof Misiukiewicz

Must not be taking: Immunotherapy, PI3K inhibitors, Dexamethasone

Disqualifiers: Pneumonitis, Cardiac disease, Psychiatric condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of a new treatment combination for individuals with advanced head and neck cancer. The treatment combines cemiplimab, a drug used for certain skin and lung cancers, with the chemotherapy drugs cisplatin and docetaxel. Participants will be divided into two groups to test different dosing schedules. Suitable candidates have locally advanced squamous cell carcinoma of the head and neck that has not been treated with chemotherapy or radiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using certain medications like strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that cemiplimab, when combined with cisplatin and docetaxel, is safe and generally easy for patients to handle. Earlier studies found this combination did not cause unexpected side effects and remained manageable for patients. Cemiplimab alone has also been well-tolerated by older patients with other health conditions.

The FDA has approved cemiplimab for treating certain skin and lung cancers, indicating its safety for those conditions. However, it is not yet approved for head and neck cancer. In the current study, researchers are specifically examining its safety for head and neck cancer, and existing evidence suggests it is likely to be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which typically involve surgery, radiation, and standard chemotherapies, the combination of Cemiplimab with chemotherapy introduces a novel approach. Cemiplimab is an immunotherapy drug that works by boosting the body's immune system to better attack cancer cells. Researchers are excited because this combination could offer a more effective treatment by potentially enhancing the immune response while simultaneously targeting cancer cells with chemotherapy. This synergy may lead to better outcomes and improved survival rates for patients compared to traditional treatments alone.

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

Research has shown that cemiplimab yields promising results in cancer treatment. It lowered the risk of cancer recurrence or death by 68% in other types, such as skin and lung cancer. In this trial, participants will receive cemiplimab combined with cisplatin and docetaxel. Researchers are testing this combination in two separate cohorts, Cohort A and Cohort B, to evaluate its safety and effectiveness for patients with advanced head and neck cancer. Early studies indicate a high response rate, with many patients experiencing a decrease in tumor size. Although cemiplimab is not yet approved for head and neck cancer, its success in similar cancers offers hope. ^{1 2 3 6 7}

Who Is on the Research Team?

Krzysztof Misiukiewicz, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage III or IV, previously untreated non-metastatic head and neck squamous cell carcinoma. Eligible patients may have had surgery but not chemotherapy or radiotherapy. They must be HPV negative or high-risk HPV positive, have a good performance status (ECOG PS 0-1), adequate organ function, and agree to use effective contraception. Exclusions include significant cardiac disease, psychiatric conditions affecting study compliance, severe allergies to docetaxel, active infections that could interfere with the study, history of certain diseases like colitis or autoimmune disorders (except vitiligo and Hashimoto's thyroiditis), prior immunotherapy treatment, and unstable brain metastases.

Inclusion Criteria

My cancer is in the mouth or throat and is either not caused by HPV or caused by a high-risk HPV type.

Predicted life expectancy >/= 12 weeks

Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria

I experience moderate numbness, pain, or tingling in my hands or feet.

I have not had a stroke or my stroke condition has been stable for the last 12 months.

Patients with history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive Cemiplimab in combination with cisplatin and docetaxel. Cohort A receives 3 cycles, and Cohort B receives 4 doses of Cemiplimab.

9 weeks

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Cisplatin
• Docetaxel

Trial Overview The trial tests two dosing schedules of cemiplimab in combination with cisplatin and docetaxel chemotherapy in patients with locally advanced head and neck cancer. Cemiplimab is approved for skin cancers but its safety for head and neck cancer is being studied here.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 3 Interventions

* In cohort B first dose of Cemiplimab will be given 7 days prior to TP followed by TP given on days 1,22,43 (+/- 2 days) and Cemiplimab given on days 14, 35, 56 (+/- 2 days). * Patient in cohort B will get 4 doses of Cemiplimab during induction therapy.

Group II: Cohort A Experimental Treatment 3 Interventions

* 3 cycles of Cemiplimab-TP induction chemotherapy will be delivered in cohort A. * Cemiplimab-TP chemotherapy will be given every 21 days starting on days 1, 22 and 43, etc. (+ 2 days) with TP given on days 1, 22, and 43 (+/- 2 days) and Cemiplimab given on days 14, 35, 56 (+/- 2 days). * Patients in cohort A will get 3 doses of Cemiplimab during induction therapy.

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?

Krzysztof Misiukiewicz

Lead Sponsor

Trials

2

Recruited

60+

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

In a study of 38 patients with locally advanced head and neck squamous cell carcinoma, the combination of docetaxel and carboplatin with radiotherapy resulted in a clinical response in 74.3% of patients, indicating effective treatment.

The regimen was generally well tolerated, with no Grade 4 toxicities reported, although common Grade 3 side effects included mucositis, xerostomia, and dysphagia, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer. Chitapanarux, I., Lorvidhaya, V., Tharavichitkul, E., et al.[2018]

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

In a phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

In a study of 77 patients with locally advanced squamous cell carcinoma of the head and neck, the concurrent chemoradiotherapy regimen using cisplatin, 5-fluorouracil, methotrexate, and leucovorin resulted in a high overall clinical response rate of 94% and a pathological complete response rate of 71%.

The treatment was generally safe and well tolerated, with significant toxicities including mucositis (39%), leukocytopenia (34%), and neutropenia (30%), indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and toxicity of chemotherapy with cisplatin, 5-fluorouracil, methotrexate and leucovorin (PFML) and radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck. Katori, H., Tsukuda, M., Taguchi, T.[2013]

Induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) significantly improves patient outcomes, providing 4.1 quality-adjusted life years (QALYs) compared to 2.0 QALYs for the standard treatment (PF).

The cost-effectiveness analysis shows that TPF has a cost of £1,782 per QALY gained compared to PF, indicating that TPF is a cost-effective option for treating locally advanced squamous cell carcinoma of the head and neck in the UK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost utility of docetaxel as induction chemotherapy followed by chemoradiation in locally advanced squamous cell carcinoma of the head and neck. Parthan, A., Posner, MR., Brammer, C., et al.[2018]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

Citations

1. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-phase-3-data-adjuvant-treatment-post

Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant ... Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, the primary endpoint of the trial (p<0.0001).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11268751/

Real-World Treatment Patterns and Outcomes of Cemiplimab ... Most cases of CSCC are cured by surgery/radiation, but an estimated 1% to 5% of patients will develop advanced disease, which is associated with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6001

Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo ... Cemiplimab is the first systemic therapy to demonstrate a statistically significant and clinically meaningful reduction in disease recurrence as adjuvant ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772611823000071

Real-world data on tolerability and clinical response of ... Cemiplimab demonstrated to be well-tolerated, even in elderly patients with severe comorbidities, achieving an objective response in 52% of patients.

5. nejm.org nejm.org/doi/pdf/10.1056/NEJMoa2502449

Adjuvant Cemiplimab or Placebo in High The current trial was successful in defining a popu- lation of patients at high risk for recurrence of cutaneous squamous-cell carcinoma as ...

6. libtayo.com libtayo.com/high-risk-cscc/study-results

LIBTAYO® (cemiplimab-rwlc) Study Results | High-Risk CSCC Discover study results and possible side effects of the adjuvant treatment of LIBTAYO® (cemiplimab-rwlc) in adults with high-risk CSCC.

7. targetedonc.com targetedonc.com/view/unpacking-the-data-behind-adjuvant-cemiplimab-s-fda-approval

Unpacking the Data Behind Adjuvant Cemiplimab's FDA ... The 24-month DFS rates for cemiplimab and placebo treatment were 87.1% and 64.1%, respectively. This effect was observed across all tumor ...