5. 2 Infusion-Related Reactions
Severe infusion-related reactions (Grade 3) occurred in 0.2% of patients receiving LIB TAYO [see Adverse
Reactions ( 6. 1)]. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the
rate of infusion or permanently discontinue LIB TAYO based on severity of reaction [see Dosage and
Administration ( 2. 2)].
5. 3 Embryo-Fetal Toxicity
Based on its mechanism of action, LIB TAYO can cause fetal harm when administered to a pregnant woman.
Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of
immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk
to a fetus. Advise females of reproductive potential to use effective contraception during treatment with
LIBTAYO and for at least 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)].
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling.
• Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions ( 5. 1)]
• Infusion-Related Reactions [see Warnings and Precautions ( 5. 2)]
6. 1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice.
The data described in WARNINGS AND PRECAU TIONS reflect exposure to LIBTAYO in 534 patients in two
open-label, single-arm, multicohort studies (Study 1423 and Study 1540), including 98 patients with metastatic
(nodal or distant) CSCC, 65 patients with locally advanced CSCC, and 371 patients with other advanced solid
tumors. LIB TAYO as a single agent or in combination with chemotherapy or radiation was administered
intravenously at doses of 1 mg/kg every 2 weeks (n= 27), 3 mg/kg every 2 weeks (n=446), 3 mg/kg every 3
weeks (n= 12), 10 mg/kg every 2 weeks (n= 6), 200 mg every 2 weeks (n= 20) or 350 mg every 3 weeks (n= 23).
Among the 534 patients, 38% were exposed for ≥ 6 months and 16% were exposed for ≥ 12 months.
The data described below reflect exposure to LIB TAYO in 163 patients with advanced CSCC (metastatic or
locally advanced disease) in Study 1423 and Study 1540. Patients received LIBTAYO 1 mg/kg every 2 weeks
(n= 1), 3 mg/kg every 2 weeks (n=139) or 350 mg every 3 weeks (n= 23) as an intravenous infusion until disease
progression, unacceptable toxicity, or completion of planned treatment. The median duration of exposure was 20
weeks ( 3 days to 1. 4 years).
The safety population characteristics were: median age of 71 years ( 38 to 96 years), 85% male, 96% white, and
ECOG performance score (PS) of 0 (44%) or 1 (56%).
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. LIB TAYO 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.
Table 2 summarizes the adverse reactions that occurred in ≥10% of patients and Table 3 summarizes Grade 3
and 4 laboratory abnormalities worsening from baseline in ≥1% of patients receiving LIB TAYO.
Table 2: Adverse Reactions in ≥10% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and
Skin and Subcutaneous Tissue
Rash* 25 1. 2
Pruritus† 15 0
Diarrhea‡ 22 0.6
Nausea 19 0
Constipation 12 0.6
General and Administration Site
Fatigue§ 29 2
Musculoskeletal and Connective Tissue
Musculoskeletal pain# 17 3
Metabolism and Nutrition
Decreased appetite 10 0
*Rash is a composite term that includes rash maculopapular, rash, dermatitis, rash generalized, dermatitis bullous, drug eruption,
erythema, rash erythematous, rash macular, rash pruritic, and skin reaction.
†Pruritus is a composite term that includes pruritus and pruritus allergic.
‡Diarrhea is a composite term that inlcudes diarrhea and colitis.
§Fatigue is a composite term that includes fatigue and asthenia.
#Musculoskeletal pain is a composite term that includes: musculoskeletal pain, back pain, myalgia, neck pain, pain in extremity.
Table 3: Grade 3 or 4 Laboratory Abnormalities Worsening from Baseline in ≥1% of Patients with Advanced
CSCC Receiving LIBTAYO in Study 1423 and Study 1540
Laboratory Abnormality Grade 3-4 (%)†
Increased aspartate aminotransferase 3
Increased INR 2
†Percentages are based on the number of patients with at least 1 post-baseline value available for that parameter.
6. 2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is
highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody
(including neutralizing antibody) positivity in an assay may be influenced by several factors including assay
methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to cemiplimab-rwlc in the studies described below
with the incidence of antibodies in other studies or to other products may be misleading.
Anti-drug antibodies (ADA) were tested in 398 of 534 patients who received LIB TAYO and the incidence of
cemiplimab-rwlc treatment-emergent ADAs was 1.3% using an electrochemiluminescent (ECL) bridging
immunoassay; 0.3% were persistent ADA responses. In the patients who developed anti-cemiplimab-rwlc
antibodies, there was no evidence of an altered pharmacokinetic profile of cemiplimab-rwlc.
8 USE IN SPECIFIC POPULATIONS
Based on its mechanism of action, LIB TAYO can cause fetal harm when administered to a pregnant woman.
There are no available data on the use of LIB TAYO in pregnant women. Animal studies have demonstrated that
inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing
fetus resulting in fetal death (see Data). Human IgG4 immunoglobulins (IgG4) are known to cross the placenta;
therefore, LIB TAYO has the potential to be transmitted from the mother to the developing fetus. Advise women of
the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal reproduction studies have not been conducted with LIB TAYO to evaluate its effect on reproduction and
fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining
maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been
shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of
administering LIB TAYO during pregnancy include increased rates of abortion or stillbirth. As reported in the
literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these
animals; however, immune-mediated disorders occurred in PD- 1 and PD-L1 knockout mice. Based on its
mechanism of action, fetal exposure to cemiplimab-rwlc may increase the risk of developing immune-mediated
disorders or altering the normal immune response.
There is no information regarding the presence of cemiplimab-rwlc in human milk, or its effects on the
breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed
children, advise women not to breastfeed during treatment and for at least 4 months after the last dose of
8.3 Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to initiating LIB TAYO [see Use in Specific
LIB TAYO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for
at least 4 months after the last dose.
8.4 Pediatric Use
The safety and effectiveness of LIB TAYO have not been established in pediatric patients.
8.5 Geriatric Use
Of the 163 patients with metastatic and locally advanced CSCC who received LIB TAYO in clinical studies, 72%
were 65 years or older and 37% were 75 years or older. No overall differences in safety or effectiveness were
observed between these subjects and younger subjects.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Immune-Mediated Adverse Reactions
Advise patients that LIB TAYO can cause immune-mediated adverse reactions including the following [see
Warnings and Precautions ( 5. 1)]:
• Pneumonitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of
pneumonitis, including new or worsening symptoms of cough, chest pain, or shortness of breath.
• Colitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of colitis,
including diarrhea, blood or mucus in stools, or severe abdominal pain.
• Hepatitis: Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatitis.
• Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of
hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus.
• Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis.
• Dermatologic Adverse Reactions: Advise patients to contact their healthcare provider immediately if they
develop a new rash.
Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related
reactions [see Warnings and Precautions ( 5. 2)].
Advise females of reproductive potential that LIB TAYO can cause harm to a fetus and to inform their healthcare
provider of a kno wn or suspected pregnancy [see Warnings and Precautions ( 5. 3) and Use in Specific Populations
Advise females of reproductive potential to use effective contraception during treatment and for at least
4 months after the last dose of LIBTAYO [see Use in Specific Populations (8.3)].
Advise female patients not to breastfeed while taking LIB TAYO and for at least 4 months after the last dose
[see Use in Specific Populations (8.2)].
© 2019 Regeneron Pharmaceuticals, Inc., and sanofi-aventis U.S. LLC.
All rights reserved. US-LIB-1492 03/19