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.
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 can occur in some tumors and can contribute to inhibition of active T-cell immune surveillance of tumors.
For intravenous use.
Indicated for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
There is. exceptional responsiveness of cutaneous squamous cell carcinoma to immunotherapy is due to a high to mutational burden due to sun related ultraviolet mutagenesis.
The recommended dosage is 350 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
Overall response rate is 47%, with the complete remission rate of 4% and a partial response of 44% with the duration a response ranging from one month to more than 15 months.
61% of patients had a duration of remission of six months or greater.
The most common adverse reactions reported in at least 20% of patients were fatigue, rash and diarrhea.
The most common Grade 3-4 adverse reactions (≥ 2%) were cellulitis, sepsis, hypertension, pneumonia, musculoskeletal pain, skin infection, urinary tract infection and fatigue.
The drug was permanently discontinued due to adverse reactions in 5% of patients; adverse reactions resulting in permanent discontinuation were pneumonitis, autoimmune myocarditis, hepatitis, aseptic meningitis, complex regional pain syndrome, cough, and muscular weakness.
Serious adverse reactions occurred in 28% of patients.
Serious adverse reactions that occurred in at least 2% of patients were cellulitis, sepsis, pneumonia, pneumonitis and urinary tract infection.
Its use has a potential for immunogenicity.
In the patients who developed anti-cemiplimab-rwlc antibodies, there was no evidence of an altered pharmacokinetic profile of cemiplimab-rwlc.
It binds to the programmed death receptor-1 (PD-1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response with the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.
Immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management are essential to ensure safe use of PD-1/PD-L1 blocking antibodies.
Immune-mediated pneumonitis occurs in 2.4% of patients.
Immune-mediated colitis occurs in 0.9% of patients.
Immune-mediated hepatitis occurs in 2.1% of patients.
Hypothyroidism occurs in 6% of patients.
Hyperthyroidism occurs in 1.5% off patients.
Type 1 diabetes mellitus, which can present with diabetic ketoacidosis, occurred in 0.7% of patients.
Immune-mediated dermatologic reactions, including erythema multiforme and pemphigoid, occurs in 1.7% of patients.
Can cause fetal harm when administered to a pregnant woman.
Can cause harm to a fetus.
Should not to breastfeed while taking LIBTAYO and for at least 4 months after the last dose.
Females of reproductive potential to use effective contraception during treatment, and for at least 4 months after the last dose.
Dose range of 1 mg/kg to 10 mg/kg administered intravenously every two weeks and 350 mg intravenously administered every three weeks.
The elimination half-life at steady state is 19 days.
Dose not affected by age, sex, body weight, race, albumin level, renal or hepatic function.
Patients received LIBTAYO 3 mg/kg intravenously every 2 weeks in studies.
In studies the overall response rate was 46-48%, CR 5.3%,
Infusion (IV) reactions that can sometimes be severe and life-threatening.
Cemiplimab-rwlc approved as the first immunotherapy for use in patients with advanced basal cell carcinoma that has previously been treated with a hedgehog pathway inhibitor (HHI) or for whom a HHI is not appropriate.
Approval for use in patients with locally advanced BCC, and for use in patients with metastatic BCC.
Phase 2 trial, which included a total of 132 patients with unresectable locally advanced BCC or metastatic BCC, either nodal or distant.
Cemiplimab elicited a confirmed objective response rate of 21% in patients with metastatic BCC and 29% in those with locally advanced BCC.
No patients with metastatic BCC achieved a complete response with the immunotherapy, while 21% achieved a partial response.
Among the patients with locally advanced BCC, 6% achieved a CR with cemiplimab and 23% achieved a PR.
Adverse effects included: fatigue, musculoskeletal pain, diarrhea, rash, pruritus, and upper-respiratory tract infection.
Thirty-two percent of patients experienced serious toxicities with the immunotherapy; including urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm, and somnolence.
Thirteen percent of patients discontinued treatment due to toxicities.
Cemiplimab-rwlc monotherapy for use in the frontline treatment of patients with advanced non–small cell lung cancer (NSCLC) with a PD-L1 expression level of 50% or higher.
Analysis of 710 patients with a PD-L1 expression of 50% or higher who had been randomized to receive the agent in the phase 3 EMPOWER-Lung 1 trial.
Cemiplimab reduced the risk of death by 32% versus chemotherapy.
The median overall survival (OS) with cemiplimab was 22 months versus 14 months with chemotherapy.
Cemiplimab was also found to improve progression-free survival (PFS) over chemotherapy.
The median PFS in the investigational arm was 6.2 months compared with 5.6 months in the control arm.
39% of patients who received cemiplimab achieved an objective response compared with 20% of those who received chemotherapy.
The median duration of response experienced with cemiplimab was 16.7 months versus 6.0 months with chemotherapy.
The median overall survival had not yet been reached in the investigative arm versus 14 months in the control arm.
The median PFS was 8 months and 6 months with cemiplimab and chemotherapy, respectively.
Toxicities that were more frequent in the cemiplimab arm over the chemotherapy arm included rash (15% vs 6%, respectively) and cough (11% vs 8%).
The most common serious adverse effects included pneumonia (5% vs 6%) and pneumonitis (2% vs 0%).
A phase 3 trial of cemiplimab (Libtayo) versus chemotherapy in patients with previously treated metastatic cervical cancer demonstrated overall survival (OS) superiority of the experimental regimen,
Treatment with cemiplimab reduced the risk of death by 31% compared with chemotherapy, with a median OS of 12.0 months versus 8.5 months, respectively.
As a monotherapy it is the first medicine to demonstrate an improvement in overall survival in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy in a phase 3 trial.
With squamous cell carcinoma there was a 27% reduction in the risk of death when treated with cemiplimab, with a median OS of 11.1 months versus 8.8 months with chemotherapy.
With adenocarcinoma, the median OS for cemiplimab and chemotherapy were 13.3 months and 7.0 months, respectively, equating to a 44% reduction in the risk of death.
Most common AEs include anemia, 25%, nausea, fatigue, vomiting and constipation.
The patient population was comprised of 78% squamous cell carcinoma and 22% adenocarcinoma, and the median patient age was 51 years.
Patients receiving cemiplimab monotherapy had treatment at a dose of 350 mg every 3 weeks.
Neoadjuvant therapy for stage II to IV cutaneous squamous cell carcinoma, with cemiplimab , is associated with a pathological complete response in a high percent of the patients with resectable cutaneous squamous cell carcinoma.