Cemiplimab for Merkel Cell Carcinoma

Overseen by Ahmad Tarhini, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Corticosteroids, Anticancer therapies, others

Disqualifiers: Concurrent malignancy, Autoimmune disease, Pregnancy, others

No Placebo Group

Breakthrough Therapy

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to determine if Cemiplimab-rwlc (called Cemiplimab in this document) given prior to tumor resection surgery is safe and effective in treating (1) Merkel Cell Carcinoma or (2) Cutaneous Squamous Cell Carcinoma (CSCC).

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 immunosuppressive therapy or have recently received certain cancer treatments, you may need to stop those before participating. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Cemiplimab for treating Merkel Cell Carcinoma?

Research shows that immune checkpoint inhibitors, like Cemiplimab, are standard treatments for advanced Merkel Cell Carcinoma, with 43% of patients experiencing a positive response to immunotherapy. This suggests that Cemiplimab, as an immune checkpoint inhibitor, may be effective for some patients with this type of cancer. ^{1 2 3 4 5}

Is cemiplimab generally safe for human use?

Cemiplimab has been shown to have acceptable safety in clinical trials for advanced cutaneous squamous cell carcinoma, with low rates of treatment discontinuation and death. Common side effects include fatigue, musculoskeletal pain, and decreased appetite, but it is generally considered safe for use in humans. ^{6 7 8 9 10}

How does the drug cemiplimab differ from other treatments for Merkel cell carcinoma?

Cemiplimab is unique because it is an immune checkpoint inhibitor, which helps the body's immune system recognize and attack cancer cells, offering a potentially longer-lasting response compared to traditional chemotherapy that often leads to rapid resistance and high toxicity. ^{3 4 11 12 13}

Research Team

Ahmad Tarhini, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with newly diagnosed or recurrent Stage I-II Merkel Cell Carcinoma, or advanced Cutaneous Squamous Cell Carcinoma. Candidates must be fit for surgery, have an ECOG status of 0-2, and agree to use effective contraception if applicable. Excluded are those with other recent cancers, certain immune conditions, severe allergies to cemiplimab components, and uncontrolled infections.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I am 18 years old or older.

If you have HIV, you can still participate if your HIV is under control and can't be detected in your blood.

Exclusion Criteria

I have a blood cancer, such as chronic lymphocytic leukemia.

I stopped taking cancer immune therapy because of its side effects.

I have an autoimmune disease treated with drugs that affect my immune system in the last 5 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive cemiplimab 350 mg IV at least 3 weeks prior to surgical resection

3 weeks

1 visit (in-person)

Post-Surgery Treatment

Participants continue to receive 350 mg cemiplimab every 3 weeks for up to 8 additional doses

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Cemiplimab-Rwlc (PD-1 Inhibitor)

Trial Overview The study tests the safety and effectiveness of Cemiplimab-Rwlc when given before tumor removal surgery in treating Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma. Participants will receive Cemiplimab prior to their scheduled surgeries.

Participant Groups

Group I: Neoadjuvant Cemiplimab Treatment Experimental Treatment 1 Intervention

Participants will receive cemiplimab 350 mg IV at least 3 weeks prior to surgical resection. After surgery they will continue to receive 350 mg cemiplimab every 3 weeks for up to 8 additional doses.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Patrick Hwu

H. Lee Moffitt Cancer Center and Research Institute

Chief Executive Officer since 2020

MD from The Medical College of Pennsylvania

Wade J. Sexton

H. Lee Moffitt Cancer Center and Research Institute

Chief Medical Officer

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

Sanofi-Synthelabo

Industry Sponsor

Trials

50

Recruited

34,700+

Findings from Research

More than 50% of patients with Merkel cell carcinoma have regional node involvement at the time of diagnosis, indicating a high likelihood of local spread rather than distant metastases.

The best treatment approach for Merkel cell carcinoma is to surgically remove the primary tumor and address regional lymph nodes, often followed by local-regional radiotherapy, which offers the highest chance of cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Merkel cell carcinoma. Mendenhall, WM., Mendenhall, CM., Mendenhall, NP.[2004]

In a study of 7,831 Merkel Cell Carcinoma (MCC) cases from the SEER registry, it was found that tumors located on the head and neck, as well as being African American or from lower income quartiles, are linked to higher mortality rates.

Patients who did not receive radiotherapy had poorer overall survival, highlighting the importance of this treatment in improving outcomes for MCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding the influence of patient demographics on disease severity, treatment strategy, and survival outcomes in merkel cell carcinoma: a surveillance, epidemiology, and end-results study. Ezaldein, HH., Ventura, A., DeRuyter, NP., et al.[2020]

In a study of 45 patients with Merkel cell carcinoma treated with immunotherapy, 43% showed an objective response, with a median response duration of 24.2 months, indicating that immunotherapy can be effective for some patients.

Factors such as less advanced disease at diagnosis and a shorter time between initial treatment and recurrence were linked to better responses to immunotherapy, while specific genetic variants in ARID2 and NTRK1 may serve as potential predictive biomarkers for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of immunotherapy benefit in Merkel cell carcinoma. Kacew, AJ., Dharaneeswaran, H., Starrett, GJ., et al.[2020]

Merkel cell carcinoma is an aggressive skin cancer primarily affecting white individuals in sun-exposed areas, with survival rates heavily influenced by the stage at diagnosis, highlighting the importance of early detection and staging evaluations like CT and PET scans.

In patients with metastatic Merkel cell carcinoma, chemotherapy regimens similar to those used for small cell lung cancer show promising response rates, with a 75% overall response rate for the CAV regimen and 60% for etoposide combined with cisplatin or carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Merkel cell carcinoma]. Viola, G., Visca, P., Bucher, S., et al.[2016]

In a multicenter phase II trial involving 50 patients with advanced Merkel cell carcinoma (MCC), pembrolizumab treatment resulted in a 58% overall response rate, with 30% achieving complete responses and a median progression-free survival of 16.8 months.

The study found that factors such as better baseline performance status, greater tumor reduction, and completion of 2 years of treatment were linked to improved survival outcomes, with a 3-year overall survival rate of 59.4% for all patients and 89.5% for responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. Nghiem, P., Bhatia, S., Lipson, EJ., et al.[2023]

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 is the first systemic treatment approved by the US FDA for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, highlighting its significance in treating this aggressive cancer.

The CASE study is a Phase IV, noninterventional study designed to gather real-world data on the clinical characteristics and survivorship of patients receiving cemiplimab, aiming to enhance understanding of its effectiveness and patient outcomes in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma. Migden, MR., Chandra, S., Rabinowits, G., et al.[2020]

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]

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]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent locally advanced or metastatic Merkel cell carcinoma (MCC) based on a study of 50 patients, showing an overall response rate of 56% and a complete response rate of 24%.

The treatment demonstrated promising durability, with 96% of responding patients maintaining their response for over 6 months, and 54% for over 12 months, although common side effects included fatigue, pain, and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. Bradford, D., Demko, S., Jin, S., et al.[2021]

In a small study of three patients with Merkel cell carcinoma treated with carboplatin and etoposide, two patients achieved partial remission, indicating that this chemotherapy combination may be effective for this rare skin cancer.

Despite initial responses, the remissions were short-lived, and two patients did not respond to subsequent chemotherapy; however, one patient achieved a complete response with a different second-line treatment combined with radiotherapy, suggesting that while Merkel cell carcinoma can respond to treatment, long-term efficacy may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide. Pectasides, D., Moutzourides, G., Dimitriadis, M., et al.[2019]

Immune checkpoint inhibitors (CPIs), like pembrolizumab, have become the standard frontline treatment for advanced Merkel Cell Carcinoma (MCC), offering durable responses with a manageable safety profile compared to traditional chemotherapy.

Research suggests that using CPIs earlier in the treatment process, such as in neoadjuvant or adjuvant settings, could further improve patient outcomes, highlighting the need for larger trials to optimize care for this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy. Marchand, A., Kervarrec, T., Bhatia, S., et al.[2021]

A patient with advanced Merkel cell carcinoma, who had previously exhausted all local and systemic treatment options, showed an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).

This case highlights the potential of TVEC as a promising treatment option for patients with aggressive and treatment-resistant Merkel cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma. Cilento, MA., Klein, O., Egan, E., et al.[2022]

References

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

Merkel cell carcinoma. [2004]

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

Understanding the influence of patient demographics on disease severity, treatment strategy, and survival outcomes in merkel cell carcinoma: a surveillance, epidemiology, and end-results study. [2020]

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

Predictors of immunotherapy benefit in Merkel cell carcinoma. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

[Merkel cell carcinoma]. [2016]

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

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. [2023]

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

Cemiplimab: First Global Approval. [2023]

7. England pubmed.ncbi.nlm.nih.gov

CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma. [2020]

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

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

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

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

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

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. [2021]

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

Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy. [2021]

13. Australia pubmed.ncbi.nlm.nih.gov

Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma. [2022]