Cemiplimab for Merkel Cell Carcinoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of Cemiplimab, an immunotherapy, when administered before and after surgery for skin cancers such as Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma. Researchers aim to determine if this treatment can reduce the cancer before surgery and prevent its recurrence afterward. Suitable participants have been diagnosed with Merkel Cell Carcinoma or specific stages of Cutaneous Squamous Cell Carcinoma and plan to undergo surgery to remove the cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that cemiplimab is generally safe. Studies have found it effective in treating certain skin cancers, with lasting results, meaning it continues to work well over time. Most patients have tolerated the treatment well. Some people have experienced side effects, but these are usually manageable.

The FDA has already approved cemiplimab for treating advanced cutaneous squamous cell carcinoma (CSCC), indicating confidence in its safety for humans. While this trial explores its use before surgery for Merkel Cell Carcinoma and CSCC, existing research on cemiplimab provides a reassuring view of its safety in other situations. This information helps set expectations for potential risks and side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cemiplimab is unique because it targets the PD-1 pathway, a mechanism that helps the immune system recognize and attack cancer cells. Unlike standard treatments for Merkel Cell Carcinoma, which may include chemotherapy and radiation, cemiplimab is an immunotherapy that leverages the body’s natural defenses to fight the cancer more precisely. Researchers are excited about cemiplimab because it offers a promising approach to potentially improve outcomes with fewer side effects compared to traditional treatments.

What evidence suggests that Cemiplimab might be an effective treatment for Merkel Cell Carcinoma or Cutaneous Squamous Cell Carcinoma?

Research has shown that Cemiplimab has strong and lasting effects in treating certain skin cancers, such as cutaneous squamous cell carcinoma (CSCC). In 2018, Cemiplimab received approval for CSCC patients who cannot undergo surgery, demonstrating its effectiveness and safety. Other studies have shown a 68% reduction in the risk of cancer returning or causing death. In this trial, participants will receive Cemiplimab as a neoadjuvant treatment for Merkel cell carcinoma, with early studies exploring its potential benefits before surgery. Overall, Cemiplimab has effectively managed skin cancers with a good safety record. ^{1 2 3 4 6}

Who Is on the Research Team?

Ahmad Tarhini, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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.

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

I am eligible for surgery to remove a large area of my cancer and possibly check nearby lymph nodes.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab-Rwlc

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.

How Is the Trial Designed?

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+

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11083599/

Efficacy and Safety of Cemiplimab for the Management of Non ... Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Abstract. Non-melanoma skin ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04975152?term=neuroendocrine+NOT+Melanoma+NOT+PMS&aggFilters=phase%3A

Study Details | NCT04975152 | Neoadjuvant Cemiplimab ... 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 ...

3. aimatskincancer.org aimatskincancer.org/press-releases/regeneron-announces-approval-of-cemiplimab-rwlc-for-adjuvant-treatment-of-cutaneous-squamous-cell-carcinoma-with-a-high-risk-of-recurrence-after-surgery-and-radiation/

Regeneron Announces Approval of Cemiplimab-rwlc for ... Cemiplimab was first approved in 2018 for patients with metastatic CSCC or locally advanced CSCC who are not eligible for curative surgery or ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08390

Neoadjuvant Cemiplimab for the Treatment of Stage I-II ... This phase I trial finds out the possible benefits and/or side effects of cemiplimab in treating patients with stage I-II Merkel cell carcinoma before surgery.

5. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-phase-3-data-adjuvant-treatment-post

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).

6. aetna.com aetna.com/cpb/medical/data/900_999/0942.html

Cemiplimab-rwlc (Libtayo) - Medical Clinical Policy Bulletins On September 28, 2018, the U.S. Food and Drug Administration (FDA) approved Libtayo cemiplimab-rwlc for the treatment of patients with metastatic cutaneous ...