Cemiplimab + Chemotherapy/Immunotherapy for Head and Neck Cancer

Recruiting at 10 trial locations

Overseen By David Pfister, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining standard chemotherapy with two immunotherapy drugs, cemiplimab and cetuximab, can safely treat head and neck cancer. The goal is to determine if this combination treatment before surgery might eliminate the need for radiation afterward. People with operable head and neck squamous cell carcinoma might be suitable candidates, especially if they haven't undergone radiation or systemic therapy before. If successful, this approach could offer a less intense treatment path after surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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.

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

Research has shown that cemiplimab, one of the treatments in this trial, is generally well-tolerated. Studies have found it effective for certain skin cancers, with usually manageable side effects. Cemiplimab is also approved for other conditions, indicating a level of safety, though individual reactions can differ.

Carboplatin, another treatment in this trial, can cause mild side effects like low blood cell counts, but serious reactions are rare. It is widely used for head and neck cancers, suggesting most patients tolerate it well.

Cetuximab is known to improve survival when combined with other treatments for head and neck cancer. Common side effects include skin reactions like rashes, which are usually mild but can be uncomfortable.

Cisplatin is also part of the treatment mix. It has a long-standing safety record in head and neck cancer but can cause side effects like nausea and kidney issues, which are often manageable with proper care.

Finally, docetaxel is used in cancer treatment and is usually well-tolerated. Some patients may experience mild side effects like fatigue or low blood counts.

Since this is an early-phase trial, the safety of this combination is still under study, but each drug has shown a generally manageable safety profile on its own. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining cemiplimab with chemotherapy and immunotherapy for head and neck cancer because it offers a fresh approach to treatment. Unlike traditional methods that mainly rely on surgery followed by radiation and chemotherapy, cemiplimab is an immunotherapy drug that helps the immune system specifically target and attack cancer cells. This combination could enhance the overall effectiveness of treatment by both directly attacking the cancer and boosting the body’s immune response. Additionally, using cemiplimab alongside drugs like carboplatin and cetuximab could potentially reduce the need for extensive surgery and minimize side effects, offering a more patient-friendly option.

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

Research has shown that cemiplimab, one of the treatments in this trial, can significantly reduce the risk of cancer recurrence or death by 68% in certain cancers, including head and neck cancer. Another treatment option, Carboplatin, has proven effective in treating certain head and neck cancers, with 80% of patients responding well. Cetuximab, also studied in this trial, works effectively when other treatments fail, particularly in head and neck cancers unresponsive to platinum-based treatments. Cisplatin, another treatment under investigation, extends patient survival when combined with other treatments for head and neck cancer. Docetaxel, also part of this trial, has shown promising results, with up to 32% of patients experiencing tumor shrinkage or stable disease. These findings suggest that using these drugs in various combinations could effectively treat head and neck cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Lara Dunn, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cemiplimab
• Cetuximab
• Cisplatin
• Docetaxel
• Post-operative radiation therapy
• Surgical Resection of Primary +/- Neck Dissection

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.

How Is the Trial Designed?

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 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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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 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 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]

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]

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 63 patients with recurrent/metastatic squamous cell carcinoma of the head and neck, the combination of carboplatin and pemetrexed demonstrated a median progression-free survival (PFS) of 5.1 months and a median overall survival (OS) of 9.4 months, indicating its efficacy as a treatment option.

Among patients with oropharyngeal cancer, particularly those with HPV-positive disease, the treatment showed even better outcomes, with a median PFS of 7.0 months and median OS of 17.1 months, highlighting the potential for improved survival in this subgroup.

NCBI (Pubmed)

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. Malhotra, B., Bellile, EL., Nguyen, NP., 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 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]

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 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 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]

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]

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. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/article-abstract/2835373

Radiotherapy With Cisplatin vs Carboplatin Paclitaxel for ... This study examines the clinical outcomes of patients with squamous cell carcinoma of the head and neck receiving carboplatin/paclitaxel vs

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1808869425000199

Definitive treatment in squamous cell carcinoma of head ... There was no significant difference between the CDDP and Carbo (79.7% vs. 81.2%; p = 1.00). These findings align with the ConCERT trial, which reported a RR of ...

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6853181/

Definitive Chemoradiotherapy With Carboplatin for ... Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2006.24.18_suppl.15534

Safety and efficacy of the combination carboplatin ... Toxicity was mild: we recorded 1 case of G3 toxicity (neutropenia) and no G4 side effects. Three pts experienced G1–2 neuropathy and 4 pts G1–2 hematologic ...

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

Locally advanced head and neck squamous cell ... Our study provides more precise data on the treatment efficacy and safety of multiple treatment regimens among LA-HNSCC patients which ...

9. go.drugbank.com go.drugbank.com/drugs/DB00958/clinical_trials?conditions=DBCOND0035874&phase=3&purpose=treatment&status=completed

Carboplatin Completed Phase 3 Trials for Squamous Cell ... Carboplatin Completed Phase 3 Trials for Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treatment ; NCT00609284. Randomized Trial of Concomitant ...