Cemiplimab Immunotherapy (LIBTAYO): Indication, Side Effects and Mechanism of Action

Cemiplimab a-k-a LIBTAYO FDA-approved checkpoint inhibitor drug for the treatment of certain cancers

Cemiplimab-rwlc a-k-a LIBTAYO is a human programmed death receptor-1 (PD-1) blocking antibody. Cemiplimab-rwlc is a recombinant human IgG4 monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2. Cemiplimab-rwlc is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Cemiplimab-rwlc has an approximate molecular weight of 146 kDa.

LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated: 

Cutaneous Squamous Cell Carcinoma (CSCC):  for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. 

Basal Cell Carcinoma (BCC): 

  • for the treatment of patients with locally advanced BCC (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.   
  • for the treatment of patients with metastatic BCC (mBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. The mBCC indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit. 

Non-Small Cell Lung Cancer (NSCLC): for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations, and is:a)locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or b) metastatic.

Side effects and Warnings of Cemiplimab Immunotherapy

Immune-Mediated Adverse Reactions 

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immunemediated nephritis and renal dysfunction, and solid organ transplant rejection. 

Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. 

Withhold or permanently discontinue LIBTAYO based on the severity of reaction.

Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue based on severity of reaction. (2.3, 5.2) 

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. (5.3) 

Embryo-Fetal Toxicity: Can cause fetal harm. 

Adverse reaction of Libtayo:

The most common adverse reactions (≥15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 laboratory abnormalities (≥2%) were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia.

Formulation of Cemiplimab:

LIBTAYO (cemiplimab-rwlc) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution with a pH of 6. The solution may contain trace amounts of translucent to white particles. Each vial contains 350 mg of cemiplimab-rwlc. Each mL contains cemiplimab-rwlc 50 mg, L-histidine (0.74 mg), L-histidine monohydrochloride monohydrate (1.1 mg), sucrose (50 mg), L-proline (15 mg), Polysorbate 80 (2 mg), and Water for Injection, USP. 12 

Mechanism of Action of Cemilimab:

Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Cemiplimab-rwlc is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. 

Pharmacokinetics of Cemiplimab

Cemiplimab-rwlc pharmacokinetic data were collected in 1062 patients with various solid tumors in a population pharmacokinetic analysis. The pharmacokinetics of cemiplimab-rwlc were linear and dose-proportional in the dose range of 1 mg/kg to 10 mg/kg LIBTAYO administered intravenously every 2 weeks. At 350 mg every 3 weeks, the mean cemiplimab-rwlc concentrations (coefficient of variation, CV%) at steady-state ranged between a minimum concentration of 61 mg/L (45%) and a maximum concentration of 171 mg/L (28%). Steady-state exposure is achieved after 4 months of treatment. In patients with CSCC, cemiplimab-rwlc steady-state exposure at 350 mg every 3 weeks was comparable to the exposure at 3 mg/kg every 2 weeks. 

Distribution The volume of distribution of cemiplimab-rwlc at steady state is 5.3 L (26%).

Elimination:  Cemiplimab-rwlc clearance (CV%) after the first dose is 0.29 L/day (33%) and decreases over time by 29%, resulting in a steady-state clearance (CLss) (CV%) of 0.20 L/day (40%). The elimination half-life (CV%) at steady state is 20.3 days (29%).