Cemiplimab for Head and Neck Squamous Cell Carcinoma

(MINIMA Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Tanguy Seiwert, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

To determine if it is feasible to use neoadjuvant immunotherapy (or immunotherapy plus chemotherapy) to reduce treatment intensity and improve long-term quality of life while maintaining very high cure rates.

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.

What data supports the effectiveness of the drug cemiplimab for head and neck squamous cell carcinoma?

While there is no direct data on cemiplimab for head and neck cancer, similar drugs like pembrolizumab and nivolumab, which target the same PD-1 pathway, have shown improved survival in patients with recurrent or metastatic head and neck squamous cell carcinoma. This suggests that cemiplimab might also be effective in treating this condition. ^{1 2 3 4 5}

Is cemiplimab safe for use in humans?

Cemiplimab has been studied in combination with other treatments for head and neck cancer, and its safety profile is consistent with previous studies of cemiplimab alone, showing no new safety concerns. ^{6 7 8 9 10}

How is the drug cemiplimab different from other treatments for head and neck squamous cell carcinoma?

Cemiplimab is unique because it is a monoclonal antibody that targets the PD-1 receptor, enhancing the immune system's ability to fight cancer by blocking signals that would otherwise inactivate immune cells. This mechanism of action is different from traditional chemotherapy or radiation, as it specifically boosts the body's natural defenses against tumors. ^{11 12 13 14 15}

Research Team

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cemiplimab (PD-1 Inhibitor)

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.

Participant Groups

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 Canada, Brazil for the following indications:

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+

Dr. William G. Nelson

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Director since 1992

MD, PhD

Dr. Elizabeth Jaffee

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Chief Medical Officer since 2023

MD

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

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]

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]

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]

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]

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 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]

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 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]

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, 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]

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 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]

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]

References

1. New Zealand 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. [2022]

2. United States 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the first-line treatment of advanced head and neck cancer. [2022]

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

Epidermal Growth Factor Receptor Inhibition in Squamous Cell Carcinoma of the Head and Neck. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. [2019]

6. 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]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

9. England 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. [2022]

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

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. [2015]

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

Cemiplimab in cutaneous squamous cell carcinomas (SCC): an overview and a clinical case. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

15. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]