Cemiplimab for Head and Neck Squamous Cell Carcinoma

(MINIMA Trial)

Overseen By Tanguy Seiwert, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Metastases, Immunodeficiency, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the new immunotherapy drug, cemiplimab, can safely reduce treatment intensity for head and neck cancer while maintaining high cure rates. It targets individuals with HPV-positive head and neck squamous cell carcinoma. The trial compares two treatment approaches: one involving surgery or low-dose radiation and another using standard treatments like surgery plus radiation or chemo-radiation. Individuals diagnosed with HPV16-positive head and neck cancer who have not yet received treatment might be suitable candidates. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

Is there any evidence suggesting that cemiplimab is likely to be safe for humans?

Research shows that the FDA has approved cemiplimab for treating certain skin cancers, such as cutaneous squamous cell carcinoma (CSCC). This approval indicates that the drug has undergone safety testing in people. In those studies, many patients tolerated cemiplimab well, though some experienced side effects like tiredness, rash, and diarrhea, which were usually manageable.

This trial is in its early stages, so while some safety information exists from other uses of cemiplimab, its effects on head and neck cancers are still being studied. Researchers will closely monitor participants to ensure their safety during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Cemiplimab is unique because it is an immunotherapy that works by targeting the PD-1 pathway, a mechanism that helps cancer cells evade the immune system. Unlike traditional treatments for head and neck squamous cell carcinoma, which often rely on surgery, chemotherapy, and radiation therapy, cemiplimab enhances the body's immune response to fight the cancer more effectively. Researchers are excited about cemiplimab because it offers a targeted approach that could potentially lead to fewer side effects and better outcomes compared to the more generalized damage caused by conventional treatments. Additionally, the trial's de-escalated therapy arm explores the possibility of reducing treatment intensity while maintaining effectiveness, which could significantly improve patients' quality of life.

What evidence suggests that cemiplimab might be an effective treatment for head and neck squamous cell carcinoma?

Studies have shown that cemiplimab can greatly lower the chance of the disease returning or causing death. One study demonstrated a 68% reduction in this risk, highlighting its effectiveness. Additionally, patients have tolerated cemiplimab well, with more than half responding positively to the treatment. This trial will evaluate cemiplimab in combination with various therapy approaches, including De-Escalated Therapy and Non/Minimally De-Escalated Therapy. These findings provide solid evidence supporting its potential in managing head and neck squamous cell carcinoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Are You a Good Fit for This Trial?

Adults with HPV-positive head and neck squamous cell carcinoma, specifically without distant metastases or prior major treatments for the cancer. Participants must have good organ function, not be pregnant or breastfeeding, and agree to use contraception. Those with active infections, other cancers needing treatment, significant heart problems, or immune system issues are excluded.

Inclusion Criteria

Must have measurable disease by RECIST 1.1 criteria.

Subjects must sign a study-specific informed consent form.

I have not had radiation or chemotherapy for head or neck cancer.

Exclusion Criteria

Intercurrent medical illnesses that would impair subject tolerance to therapy or limit survival.

Pregnant and nursing women.

I have an active case of tuberculosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 3 cycles/9 weeks of Cemiplimab (IV infusion) with or without Carboplatin/Paclitaxel based on measurable benefit

9 weeks

Weekly assessments by multidisciplinary team

Curative Treatment

Participants receive either de-escalated treatment (TORS or Low Dose Radiation Therapy) or non-minimally de-escalated treatment (Surgery + Post-Operative Radiation Therapy or 60 Gy Chemoradiation Therapy)

Varies based on treatment type

Adjuvant Treatment

Adjuvant Cemiplimab for 4 months (5 doses every 21 days) following curative intent treatment

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of HPV ctDNA clearance and immune response

Up to 18 months post locoregional therapy

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab

Trial Overview The trial is testing Cemiplimab alone or combined with chemotherapy in patients before surgery to see if it can reduce the intensity of later treatments while maintaining high cure rates. The goal is also to improve long-term quality of life for these patients.

How Is the Trial Designed?

Group I: Non/Minimally De-Escalated Therapy Experimental Treatment 1 Intervention

Surgery + Post-Operative Radiation Therapy (PORT) or 60 Gy Chemo-Radiation Therapy (CRT)

Group II: De-Escalated Therapy Experimental Treatment 1 Intervention

Surgery (TORS) or Low-dose Radiation Therapy (42 Gy)

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

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]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study involving 32 patients with advanced head and neck cancer, the addition of cetuximab to a treatment regimen of paclitaxel, carboplatin, and radiation was found to increase dermatologic toxicities, with 44% experiencing grade 3 radiation dermatitis.

Despite the increased skin toxicity, the combination treatment did not lead to higher mucosal toxicity compared to previous studies, suggesting that while cetuximab may enhance side effects, it does not worsen certain other adverse effects associated with cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. Birnbaum, A., Dipetrillo, T., Rathore, R., et al.[2015]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[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]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

Cemiplimab, an anti-PD-1 monoclonal antibody, has been shown to be effective in treating locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC), as demonstrated in a clinical case of an elderly woman who responded well after just one course of therapy.

The treatment was well tolerated, highlighting the potential of immunotherapy as a promising option for patients with cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in cutaneous squamous cell carcinomas (SCC): an overview and a clinical case. Ghidini, A., Santangelo, D., Vaccaro, G., et al.[2022]

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]

Patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, but new treatments targeting specific pathways are emerging.

Cetuximab, pembrolizumab, and nivolumab are FDA-approved therapies that target the epidermal growth factor receptor and PD-1, respectively, showing promise in improving treatment outcomes for R/M HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies. Moreira, J., Tobias, A., O'Brien, MP., et al.[2022]

Pembrolizumab has become the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), showing improved overall survival compared to traditional therapies like the EXTREME regimen.

The effectiveness of pembrolizumab is influenced by the PD-L1 expression level, with monotherapy recommended for patients with a PD-L1 combined positive score (CPS) ≥1, while those with lower CPS may benefit from the EXTREME regimen, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the first-line treatment of advanced head and neck cancer. de Sousa, LG., Ferrarotto, R.[2022]

Cetuximab, an anti-EGFR monoclonal antibody, significantly enhances the effectiveness of radiotherapy in treating squamous cell carcinoma of the head and neck, leading to better locoregional control and improved survival rates compared to radiotherapy alone.

Despite its benefits, only a small percentage of patients respond to anti-EGFR therapies, highlighting the need for further research into the mechanisms of treatment resistance and the development of predictive biomarkers to identify which patients are most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal Growth Factor Receptor Inhibition in Squamous Cell Carcinoma of the Head and Neck. Machiels, JP., Schmitz, S.[2019]

Citations

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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. regeneron.com regeneron.com/downloads/libtayo_fpi.pdf

LIBTAYO® Full Prescribing Information LIBTAYO is indicated for the adjuvant treatment of adult patients with CSCC at high risk of recurrence [see Clinical Studies (14.1)] after surgery and radiation ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761097s014lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use What is LIBTAYO? LIBTAYO is a prescription medicine used to treat: • people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC).

8. libtayohcp.com libtayohcp.com/cscc

LIBTAYO® (cemiplimab-rwlc) in Advanced CSCC LIBTAYO is the FIRST treatment indicated for patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC)

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04831450

NCT04831450 | Phase 2 Trial of Maintenance Cemiplimab ... The purpose of this study is to evaluate the experimental immunotherapy agent cemiplimab-rwlc when given after completion of chemotherapy and radiation ...