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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine the safety and tolerability of two dosing schedules of cemiplimab given in combination with cisplatin and docetaxel induction chemotherapy (TPI) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Cemiplimab is FDA approved for treatment of basal cell and squamous cell carcinoma of the skin as well as non-small cell lung cancer but not for squamous cell carcinoma of head and neck.

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.

What data supports the effectiveness of the drug combination of Cemiplimab, Cisplatin, and Docetaxel for head and neck cancer?

Research shows that combining Docetaxel and Cisplatin is effective in treating head and neck cancer, with response rates of 33% to 44% and improved survival when Docetaxel is added to Cisplatin and 5-fluorouracil. This suggests potential effectiveness when combined with Cemiplimab. ^{1 2 3 4 5}

Is the combination of Cemiplimab, Cisplatin, and Docetaxel safe for treating head and neck cancer?

Studies have shown that Docetaxel and Cisplatin, when used together, have been tested for safety in treating head and neck cancer. These studies found the combination to be feasible, but they also evaluated the side effects (toxicity) to ensure it is safe for patients. ^{3 5 6 7 8}

How is the drug Cemiplimab combined with chemotherapy different for head and neck cancer?

Cemiplimab combined with chemotherapy, including cisplatin and docetaxel, is unique because it adds an immunotherapy component (Cemiplimab) to the treatment, which may enhance the body's immune response against cancer cells, potentially offering a new approach compared to traditional chemotherapy alone. ^{1 2 5 6 9}

Research Team

Krzysztof Misiukiewicz, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

References

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

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

2. England 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). [2022]

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

Induction docetaxel and S-1 followed by concomitant radiotherapy with low-dose daily cisplatin in locally advanced head and neck carcinoma. [2018]

4. United States 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. [2018]

5. England 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. [2020]

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

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

[A Phase II study of docetaxel and cisplatin in patients with recurrent or unresectable squamous cell carcinoma of the head and neck]. [2018]

9. Germany 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. [2013]