Cemiplimab Clinical Trials

What Is Cemiplimab?

Cemiplimab (brand name Libtayo) is an FDA-approved medication for cutaneous squamous cell carcinoma (CSCC). It is an immunotherapy drug that works by targeting a protein called PD-1, acting as an immune checkpoint inhibitor. By blocking PD-1, cemiplimab helps to stimulate the body's immune system to recognize and fight cancer cells.

Cemiplimab is also being investigated for use in a wide range of other cancers and conditions. Clinical trials involving cemiplimab have enrolled a total of 31,624 participants across 198 studies, with the earliest trial starting in 2010 and the latest projected to conclude in 2026.

Uses and Conditions Under Study

Cemiplimab is being studied for its potential to treat various cancers, often by itself or in combination with other therapies. The drug's mechanism of stimulating the immune system makes it a candidate for many types of tumors.

• Skin Cancers: Beyond its approved use in cutaneous squamous cell carcinoma (CSCC), cemiplimab is extensively studied for other skin cancers. It is being investigated in 16 trials for CSCC, 12 trials for melanoma, and 5 trials for basal cell carcinoma (BCC). In CSCC, cemiplimab is being explored for advanced, unresectable, or metastatic forms, and in combination with surgery and radiation for resectable stage III/IV disease. For BCC, studies are combining cemiplimab with local treatments like imiquimod to enhance immune response.
• Lung Cancers: Cemiplimab is a focus in 7 trials for non-small cell lung cancer (NSCLC). Research includes combining cemiplimab with chemotherapy before surgery in stage 3 NSCLC, and evaluating its use with reduced-dose chemotherapy in older or frail patients. It is also being studied with novel agents like THIO, a telomere targeting agent, for NSCLC.
• Head and Neck Cancers: There are 8 trials for head and neck squamous cell carcinoma (HNSCC) and 6 trials for general head and neck cancer. Studies are determining the safety and tolerability of cemiplimab with induction chemotherapy in locally advanced HNSCC.
• Other Solid Tumors: Cemiplimab is being investigated in 6 trials for advanced solid tumors and 5 trials for prostate cancer. Other conditions under study include biliary tract cancer, adrenocortical carcinoma, malignant glioma, and estrogen receptor positive (ER+) breast cancer.
• Hematologic Malignancies: Cemiplimab is also being explored in combinations for various blood cancers, including multiple myeloma, diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), and classical Hodgkin lymphoma (cHL).
• HIV-1: Cemiplimab's immunotherapeutic activity has been evaluated in participants with HIV-1 who are on combination antiretroviral therapy.

Dosing

Cemiplimab is typically administered intravenously (IV) or subcutaneously (SC) and has been studied in various strengths and schedules, often in combination with other medications.

Commonly studied intravenous doses include:

• 350 mg every 3 weeks (Q3W)
• 600 mg every 4 weeks (Q4W)
• 3 mg/kg every 2 weeks (Q2W)

A subcutaneous formulation of 350 mg Q3W has also been investigated. In clinical trials, cemiplimab is frequently given as a monotherapy or in combination with other drugs such as chemotherapy, fianlimab, ipilimumab, or targeted agents. Specific investigational doses like 0.3 mg/kg, 1 mg/kg, and 3 mg/kg have been explored to determine optimal biological doses in various study arms.

Side Effects

In a clinical trial involving a small number of patients (4 participants) taking Cemiplimab compared to placebo, the most commonly reported side effects where Cemiplimab showed a higher rate included:

• Proteinuria (excess protein in urine): 50.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Rhinorrhoea (runny nose): 50.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Decreased blood thyroid stimulating hormone (TSH): 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Increased blood uric acid: 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Cough: 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Decreased creatinine renal clearance (a measure of kidney function): 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Drug-induced liver injury: 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.
• Fatigue: 25.0% of patients on Cemiplimab experienced this, compared to 0.0% on placebo.

It is important to note that these figures are based on a very limited number of participants, and larger studies may show different frequencies.

Clinical Trial Results

Advanced Cutaneous Squamous Cell Carcinoma (CSCC)

In a study (NCT02760498) of Cemiplimab in patients with advanced cutaneous squamous cell carcinoma, different dosing regimens were evaluated. The study included patients with metastatic CSCC (mCSCC) and locally advanced CSCC (laCSCC).

• Overall Response Rate (ORR): When assessed by an independent review, the ORR for patients receiving Cemiplimab was 50.8% for mCSCC (3 mg/kg every 2 weeks), 44.9% for laCSCC (3 mg/kg every 2 weeks), 46.4% for mCSCC (350 mg every 3 weeks), and 61.9% for mCSCC and laCSCC (600 mg every 4 weeks).
• Complete Response (CR) Rate: The rate of complete response was 20.3% for mCSCC (3 mg/kg every 2 weeks), 12.8% for laCSCC (3 mg/kg every 2 weeks), 19.6% for mCSCC (350 mg every 3 weeks), and 22.2% for mCSCC and laCSCC (600 mg every 4 weeks).
• Duration of Response (DOR): For patients with laCSCC receiving 3 mg/kg every 2 weeks, the median duration of response was 41.9 months. For mCSCC patients receiving 350 mg every 3 weeks, the median DOR was 41.3 months.
• Progression-Free Survival (PFS): The median PFS was 18.4 months for mCSCC (3 mg/kg every 2 weeks), 18.5 months for laCSCC (3 mg/kg every 2 weeks), 21.7 months for mCSCC (350 mg every 3 weeks), and 32.2 months for mCSCC and laCSCC (600 mg every 4 weeks).
• Overall Survival (OS): The median overall survival was 57.7 months for mCSCC patients receiving 3 mg/kg every 2 weeks, and 48.4 months for mCSCC patients receiving 350 mg every 3 weeks.

Advanced Basal Cell Carcinoma (BCC)

In a study (NCT03132636) of Cemiplimab for advanced basal cell carcinoma in patients who had progressed on or were intolerant to Hedgehog Pathway Inhibitor therapy:

• Objective Response Rate (ORR): Independent central review showed an ORR of 22.2% for metastatic BCC (mBCC) and 32.1% for unresectable locally advanced BCC (laBCC).
• Complete Response (CR) Rate: The complete response rate was 3.7% for mBCC and 8.3% for laBCC.
• Progression-Free Survival (PFS): The median PFS was 10.1 months for mBCC and 16.5 months for laBCC.
• Overall Survival (OS): For mBCC patients, the median OS was 49.9 months.
• Patient-Reported Outcomes: Patients generally reported improvements in skin symptoms as measured by the Skindex-16 Questionnaire.

Cervical Cancer

A study (NCT03257267) compared Cemiplimab to investigator's choice chemotherapy in adults with cervical cancer.

• Overall Survival (OS): Patients treated with Cemiplimab had a median OS of 11.7 months, compared to 8.5 months for those on investigator's choice chemotherapy. For the squamous cell carcinoma (SCC) population, median OS was 10.9 months

  Currently Recruiting Trials

  Cemiplimab is currently being investigated in numerous clinical trials across various cancer types, exploring its potential as a standalone treatment or in combination with other therapies. These studies aim to understand how cemiplimab works, its safety, and its effectiveness for patients.

  One such trial, NCT07147231, is a Phase 1/Phase 2 study sponsored by the National Cancer Institute (NCI). It is testing cemiplimab in combination with pidnarulex (CX-5461) for treating refractory microsatellite stable colorectal cancer. This trial is enrolling up to 86 participants with metastatic, refractory, or unresectable Stage III or IV colorectal adenocarcinoma.

  Another NCI-sponsored Phase 2 trial, NCT07281417, is evaluating the addition of cemiplimab to chemotherapy (carboplatin and paclitaxel) given before surgery for patients with sinonasal squamous cell carcinoma. This study plans to enroll 108 participants with Stage III, IVA, or IVB sinonasal cancer.

  For patients with head and neck cancer, NCT06980038 is a Phase 2 NCI-sponsored trial comparing cemiplimab alone versus cemiplimab combined with CDX-1140 prior to surgery. This trial is recruiting 44 participants with Stage III-IV head and neck squamous cell carcinoma, including various recurrent forms.

  In non-small cell lung cancer (NSCLC), the ETOP IBCSG Partners Foundation is sponsoring NCT06931717, a Phase 3 study assessing cemiplimab as an adjuvant immunotherapy after surgery for patients who have not received prior chemotherapy. This trial has an enrollment target of 390 participants.

  A Phase 2 study, NCT07188896, led by Brian Rini, is a randomized trial investigating cemiplimab and fianlimab, with or without ipilimumab, as a first-line treatment for advanced renal cell carcinoma. This trial aims to enroll 120 participants with advanced, metastatic, or clear cell renal cell carcinoma.

  Regeneron Pharmaceuticals is sponsoring NCT06585410, a Phase 3 study of intralesional cemiplimab for adult patients with early-stage cutaneous squamous cell carcinoma (CSCC). This trial is designed to enroll 369 participants.

  Finally, NCT06413680, sponsored by Regeneron Pharmaceuticals, is a Phase 1/Phase 2 first-in-human study exploring REGN10597 alone or in combination with cemiplimab for adult participants with advanced solid tumors. This study is recruiting up to 240 individuals with various advanced solid tumors, including melanoma and clear cell renal cell carcinoma.

  Where to Participate

  Clinical trials involving cemiplimab are widely accessible, with study sites spanning across the United States. There are 824 locations in 448 cities across 49 states, offering many opportunities for participation.

  The cities with the most active recruiting sites include:

  • New York, New York (26 sites)
  • Portland, Oregon (17 sites)
  • Pittsburgh, Pennsylvania (16 sites)
  • Boston, Massachusetts (15 sites)
  • Los Angeles, California (15 sites)
  • Houston, Texas (14 sites)
  • Columbus, Ohio (14 sites)

  Eligibility for these trials generally includes individuals aged 12 to 100 years, of all genders. Healthy volunteers are not typically sought for these studies, but children may be eligible for some trials.

  Development Timeline

  The development journey for cemiplimab began with its first trial on January 5, 2010. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia. However, its development significantly expanded into oncology, where it is primarily known today as an anti-PD-1 immunotherapy.

  Regeneron Pharmaceuticals has been a leading sponsor, driving 46 of the 198 total trials conducted for cemiplimab. Other notable sponsors include M.D. Anderson Cancer Center and the National Cancer Institute (NCI). The research pipeline has steadily grown, encompassing a broad range of cancers, including Head and Neck Squamous Cell Carcinoma, Non-Small Cell Lung Cancer, Basal Cell Carcinoma, Prostate Cancer, and Ovarian Cancer.

  The clinical development program has enrolled over 31,624 participants across various phases. The majority of trials have been in Phase 2, with 101 studies, followed by Phase 1 (37 trials) and Phase 1/Phase 2 (36 trials). As of the latest data, 11 trials have reached Phase 3, indicating advanced stages of investigation. The latest trial is projected to conclude on May 5, 2026, reflecting ongoing commitment to understanding cemiplimab's full therapeutic potential.