Cemiplimab + Chemotherapy/Immunotherapy for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

+10 other locations

Overseen by Lara Dunn, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Immunosuppressants, Live vaccines

Disqualifiers: Prior radiation, Autoimmune disorders, Uncontrolled infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether combining the standard chemotherapy for head and neck cancer with the immunotherapy drugs cetuximab and cemiplimab (the study drug) is a safe treatment for head and neck cancer, and whether receiving this combination treatment before surgery may allow participants to forgo the standard radiation treatment after surgery.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressant medications, you may need to stop them at least 14 days before starting the trial treatment.

What data supports the effectiveness of the drugs used in the Cemiplimab + Chemotherapy/Immunotherapy for Head and Neck Cancer trial?

Research shows that cisplatin is effective for head and neck cancer, especially for HPV-associated cases, and carboplatin is an alternative for those who can't use cisplatin. Additionally, a combination of carboplatin, cetuximab, and immune checkpoint inhibitors like pembrolizumab has shown high response rates in patients with recurrent or metastatic head and neck cancer. ^{1 2 3 4 5}

Is the combination of Cemiplimab and chemotherapy/immunotherapy safe for head and neck cancer patients?

The safety profile of Cemiplimab in combination with other treatments for head and neck cancer is consistent with its use as a single treatment, with no new safety concerns reported. In studies involving similar combinations, common side effects included mild to moderate issues like anemia (low red blood cell count), neutropenia (low white blood cell count), and hypertension (high blood pressure), with more severe side effects occurring less frequently. ^{6 7 8 9 10}

What makes the drug combination of Cemiplimab, Carboplatin, Cetuximab, Cisplatin, and Docetaxel unique for head and neck cancer?

This drug combination is unique because it combines multiple approaches: Cemiplimab, an immune checkpoint inhibitor, with chemotherapy agents like Carboplatin, Cisplatin, and Docetaxel, and Cetuximab, which targets the epidermal growth factor receptor. This multi-faceted approach aims to enhance the immune response while directly attacking cancer cells, potentially offering a more comprehensive treatment for head and neck cancer. ^{4 5 11 12 13}

Research Team

Lara Dunn, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with certain types of head and neck cancer that can be surgically removed. They must have good blood counts, organ function, no distant metastasis, and not have had prior radiation or systemic therapy for the cancer. Excluded are those with recent serious infections, autoimmune disorders treated in the last 5 years (with some exceptions), live vaccines taken within a month, HIV/HBV/HCV unless controlled, history of immune-related pneumonitis or solid organ transplant.

Inclusion Criteria

My liver tests are within normal limits, or slightly above if I have Gilbert syndrome.

I am over 18 years old.

My kidney function is within the normal range.

Exclusion Criteria

I have had radiation and medication treatment for head or neck cancer.

I have not received a live vaccine in the last 30 days.

My oral cancer cannot be removed with surgery or I am not fit for surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab

6-8 weeks

Surgery

Participants undergo definitive surgery for head and neck squamous cell carcinoma

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Cemiplimab (Monoclonal Antibodies)
• Cetuximab (Monoclonal Antibodies)
• Cisplatin (Chemotherapy)
• Docetaxel (Chemotherapy)
• Post-operative radiation therapy (Radiation)
• Surgical Resection of Primary +/- Neck Dissection (Procedure)

Trial Overview The study tests if combining standard chemotherapy with immunotherapy drugs cetuximab and cemiplimab before surgery is safe and effective enough to potentially skip post-surgery radiation. Participants will receive this combination treatment to see how well it works against head and neck cancers.

Participant Groups

Group I: Secondary Cohort Experimental Treatment 3 Interventions

Participants with locally advanced, resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.

Group II: Head and Neck Squamous Cell Cancer/HNSCC Experimental Treatment 8 Interventions

Participants with locally advanced, resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

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

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 study of 1,149 patients with advanced head and neck squamous cell carcinoma, carboplatin-based chemoradiotherapy showed similar cancer-specific mortality rates compared to cisplatin-based therapy, indicating that carboplatin can be an effective alternative for patients unable to receive cisplatin.

Both carboplatin and cisplatin-based chemoradiotherapy were found to be more effective than radiation therapy alone or radiation with cetuximab, suggesting that carboplatin should be further investigated as a viable treatment option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Xiang, M., Colevas, AD., Holsinger, FC., et al.[2020]

In a study involving 16 patients with head and neck cancer, the combination of docetaxel and carboplatin during radiotherapy resulted in a high complete response rate of 81%, indicating strong efficacy in treating this type of cancer.

While the treatment was effective, it also led to significant toxicities, including grade 3 mucositis in 69% of patients, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. Karasawa, K., Shinoda, H., Katsui, K., et al.[2018]

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]

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]

Cemiplimab combined with radiation therapy, cyclophosphamide, and GM-CSF did not show improved efficacy compared to standard PD-1 inhibitor monotherapy in treating refractory and metastatic head and neck squamous cell carcinoma, based on a study of 15 patients.

The safety profile of the combination therapy was consistent with previous findings for cemiplimab alone, with no new safety concerns identified, although common side effects included fatigue and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Babiker, H., Brana, I., Mahadevan, D., et al.[2021]

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

In a study involving 201 patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the two-drug regimen of cetuximab plus cisplatin (CetCis) demonstrated noninferior progression-free survival (PFS) compared to the three-drug regimen that included paclitaxel (CetCisPac), with median PFS of 6 months versus 7 months, respectively.

The CetCis regimen also showed a lower rate of grade 4 toxicities (14% compared to 33% in the CetCisPac group), indicating a potentially safer treatment option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Bossi, P., Miceli, R., Locati, LD., et al.[2023]

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]

References

1. 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]

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

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. [2020]

3. Greece pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. [2018]

4. Switzerland 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries. [2020]

6. 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]

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

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

8. Greece 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

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

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. [2023]

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

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

13. 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]