Cemiplimab for Merkel Cell Carcinoma
Recruiting in Palo Alto (17 mi)
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.12345
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.678910
How does the drug cemiplimab differ from other treatments for Merkel cell carcinoma?
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.
See 9 more
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.
See 19 more
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 OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant Cemiplimab TreatmentExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Regeneron PharmaceuticalsIndustry Sponsor
Sanofi-SynthelaboIndustry Sponsor
References
Merkel cell carcinoma. [2004]To determine the natural history and treatment outcomes for patients with Merkel cell carcinoma.
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]To identify trends in patient presentation and outcomes data that may guide the development of clinical algorithms on Merkel Cell Carcinoma (MCC).
Predictors of immunotherapy benefit in Merkel cell carcinoma. [2020]Merkel cell carcinoma is a rare cancer for which immune checkpoint blockade is standard-of-care for recurrent/metastatic disease. However, not all patients benefit from immunotherapy. A greater understanding of molecular mechanisms and predictive biomarkers are unmet needs. We retrospectively analyzed electronic health records and next-generation sequencing data of 45 patients treated at our institution from 2013 to 2020 to understand clinical and genomic correlates of benefit from immunotherapy. Our cohort predominantly included individuals with stage III disease at primary disease diagnosis and individuals with stage IV disease at recurrent/metastatic disease diagnosis. Most received immunotherapy as first-line treatment. 43% experienced objective response (median duration of response 24.2 months, 95% confidence interval 8.8-not reached). Median overall survival was 15.5 months (95% confidence interval 9.0-28.7) (median follow-up 25.2 months). Less advanced stage at primary disease diagnosis and shorter disease-free interval between completion of initial treatment and recurrence were each associated with greater odds of response (odds ratio of 0.06, p = 0.04 for stage; odds ratio 0.75, p = 0.05 for disease-free interval). Single-nucleotide variants in ARID2 and NTRK1 were associated with response (p = 0.05, without Bonferroni correction), while none of Merkel cell polyomavirus status, total mutational burden, ultraviolet mutational signatures, and copy-number alterations predicted outcomes. Patients with shorter disease-free interval may be particularly suitable immunotherapy candidates. Our molecular findings point to ARID2 and NTRK1 as potential predictive markers and/or therapeutic targets (e.g., with Trk inhibitors), although this association needs to be confirmed in a larger sample.
[Merkel cell carcinoma]. [2016]Merkel cell carcinoma is a rare form of skin cancer of likely neuroendocrine origin wich affects mainly white population in sun-exposed areas. It is an aggressive tumor and survival is dependent on stage at the time of diagnosis. The staging evaluation include CT imaging and recently PET scan. Surgical excision with or without lymph node dissection, followed by postoperative radiotherapy in stage II disease, is the standard treatment of non metastatic disease. The role of adjuvant chemotherapy is still controversial. In patients with metastatic disease, chemotherapy regimens active in small cell lung cancer are generally used. The combination of cyclophosphamide, doxorubicin and vincristine (CAV) has an overall response rate of 75%, whereas the response rate of etoposide in combination with cisplatin or carboplatin is 60%. Experience with other therapeutic agents, such as tumor necrosis factor, interferon and octreotide is scanty. Recently, encouraging preliminary results with targeted agents have been reported. Our experience in 14 patients, four of whom treated with chemotherapy for advanced disease, is in agreement with literature
Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. [2023]Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.
Cemiplimab: First Global Approval. [2023]Cemiplimab (LIBTAYO®; cemiplimab-rwlc), a human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Regeneron Pharmaceuticals and Sanofi Genzyme. The drug is being investigated as a treatment for various cancers and in September 2018 received approval in the USA for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. This article summarizes the milestones in the development of cemiplimab leading to this first global approval for the treatment of advanced cutaneous squamous cell carcinoma.
CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma. [2020]In 2018, cemiplimab-rwlc became the first systemic treatment approved by the US FDA for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In 2019, conditional approvals were granted by Health Canada and the European Commission for the same indications. Limited data exist pertaining to the clinical characteristics, disease progression and survivorship of patients with advanced CSCC in real-world clinical practice. CemiplimAb-rwlc Survivorship and Epidemiology (CASE) is a prospective Phase IV, noninterventional, survivorship and epidemiology study that will enroll patients with advanced CSCC who have recently initiated or who plan to receive cemiplimab in a real-world setting. Trial registration number: NCT03836105.
Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.
Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]Cemiplimab, a high-affinity, highly potent human monoclonal antibody that binds to the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) receptor, is the only drug to attain Food and Drug Administration (FDA) approval and marketing authorization from the European Commission for use in patients with metastatic and locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation therapy as a first- or later-line treatment. In pivotal phase II clinical testing, cemiplimab showed rapid and substantial antitumor efficacy and acceptable safety. This systematic review was aimed at evaluating the efficacy and safety of cemiplimab in patients with advanced CSCC. To this end, I reviewed EMBASE, MEDLINE, PubMed, and clinical trial registries/databases by using the following keywords alone or in combination: "cemiplimab," "Libtayo," "cutaneous squamous cell carcinoma," "REGN2810," and "SER439684." Cemiplimab showed clinical efficacy and considerable safety and was associated with low rates of treatment discontinuation (7%) and death (3%). However, the current recommendation is primarily based on only phase II clinical testing due to the absence of an approved comparator agent.
FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. [2021]On December 19, 2018, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co. Inc., Whitehouse Station, NJ) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Approval was based on Cancer Immunotherapy Trials Network protocol 9, also known as KEYNOTE-017 (NCT02267603), a multicenter, nonrandomized, open-label trial that enrolled 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. The major efficacy outcome measures were overall response rate (ORR) and response duration assessed by blinded independent central review per RECIST 1.1. The ORR was 56% (95% confidence interval: 41, 70) with a complete response rate of 24%. The median response duration was not reached. Among the 28 patients with responses, 96% had response durations of greater than 6 months and 54% had response durations of greater than 12 months. The most common adverse reactions of pembrolizumab reported in at least 20% of patients who received pembrolizumab as a single agent were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for the Food and Drug Administration's accelerated approval of pembrolizumab for the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma, including efficacy and safety information. This approval provides patients and physicians with an additional treatment option for this aggressive and life-threatening carcinoma.
Chemotherapy for Merkel cell carcinoma with carboplatin and etoposide. [2019]Merkel cell carcinoma is a rare malignant tumor of the skin. We treated three patients with Merkel call carcinoma with the combination of carboplatin and etoposide, which have been mostly used in the treatment of small cell lung carcinoma. Two patients experienced partial remission of short duration. The third patient received the combination on an adjuvant basis but relapse occurred briefly. Two of these patients failed to respond to second-line chemotherapy with cisplatin, ifosfamide, and epirubicin. The patient who had the first-line treatment on an adjuvant basis, responded completely with the second-line chemotherapy plus radiotherapy and remains disease-free for 5+months. Merkel cell carcinoma appears to be a sensitive tumor to chemotherapeutic regimens used for small cell lung carcinoma, but the responses are often brief.
Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy. [2021]Merkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As with other cancers, immune checkpoint inhibitors (CPI), including pembrolizumab, allow durable responses with a manageable safety profile in these patients.
Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma. [2022]Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous tumour of neuroendocrine cell origin, which can grow rapidly and metastasise early. Localised disease is treated with surgery and radiotherapy. Disease that reaches a more advanced stage can be treated with a variety of different treatment modalities including surgery, radiotherapy, chemotherapy, radionuclide therapy, immunotherapy, and intralesional therapy. We report a case of a patient who had exhausted all local and systemic treatment options and who subsequently had an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).