Cemiplimab-rwlc Injection

Name: Cemiplimab-rwlc Injection

Indications

LIBTAYO is 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.

How supplied

Dosage Forms And Strengths

Injection: 350 mg/7 mL (50 mg/mL), clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles in a single-dose vial.

Storage And Handling

LIBTAYO (cemiplimab-rwlc) injection is a clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles. It is supplied in a carton containing 1 single-dose vial of:

250 mg/5 mL (50 mg/mL) (NDC 61755-007-01)
350 mg/7 mL (50 mg/mL) (NDC 61755-008-01)

Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Protect from light. Do not freeze or shake.

Manufactured by: Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591-6707. Marketed by: Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591) and sanofi-aventis U.S. LLC (Bridgewater, NJ 08807), Revised: Sep 2018

Side effects

The following serious adverse reactions are described elsewhere in the labeling.

  • Severe and Fatal Immune-Mediated Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]

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 PRECAUTIONS 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. LIBTAYO 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 LIBTAYO in 163 patients with advanced CSCC (metastatic or locally advanced disease) in Study 1423 and Study 1540 [see Clinical Studies]. 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. LIBTAYO 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 LIBTAYO.

Table 2: Adverse Reactions in ≥ 10% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540

Adverse Reactions LIBTAYO
N=163
All Grades % Grade 3-4 %
Skin and Subcutaneous Tissue
Rash* 25 1.2
Pruritus† 15 0
Gastrointestinal
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 includes 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 (%)†
Chemistry
Increased aspartate aminotransferase 3
Increased INR 2
Hypoalbuminemia 1
Hematology
Lymphopenia 7
Anemia 2
Electrolytes
Hypophosphatemia 4
Hyponatremia 3
Hypercalcemia 1
† Percentages are based on the number of patients with at least 1 post-baseline value available for that parameter.

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 LIBTAYO 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.

Patient information

LIBTAYO®
(Lib-TIE-oh)
(cemiplimab-rwlc) injection

What is the most important information I should know about LIBTAYO?

LIBTAYO is a medicine that may treat a type of skin cancer by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include:

  • new or worsening cough
  • shortness of breath
  • chest pain

Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include:

  • diarrhea (loose stools) or more frequent bowel movements than usual
  • stools that are black, tarry, sticky, or have blood or mucus
  • severe stomach-area (abdomen) pain or tenderness

Liver problems (hepatitis). Signs and symptoms of hepatitis may include:

  • yellowing of your skin or the whites of your eyes
  • severe nausea or vomiting
  • pain on the right side of your stomach area (abdomen)
  • drowsiness
  • dark urine (tea colored)
  • bleeding or bruising more easily than normal
  • feeling less hungry than usual

Hormone gland problems (especially the adrenal glands, pituitary, thyroid, and pancreas). Signs and symptoms that your hormone glands are not working properly may include:

  • headache that will not go away or unusual headaches
  • rapid heart beat
  • increased sweating
  • extreme tiredness
  • weight gain or weight loss
  • dizziness or fainting
  • feeling more hungry or thirsty than usual
  • hair loss
  • feeling cold
  • constipation
  • your voice gets deeper
  • very low blood pressure
  • urinating more often than usual
  • nausea or vomiting
  • stomach-area (abdomen) pain
  • changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems, including nephritis and kidney failure. Signs of these problems may include:

  • decrease in your amount of urine
  • blood in your urine
  • swelling in your ankles
  • loss of appetite

Skin problems. Signs of these problems may include:

  • rash
  • itching
  • skin blistering
  • painful sores or ulcers in mouth or nose, throat, or genital area

Problems in other organs. Signs of these problems may include:

  • headache
  • tiredness or weakness
  • sleepiness
  • changes in heartbeat, such as beating fast, or seeming to skip a beat, or pounding sensation
  • seeing or hearing things that are not there (hallucinations)
  • severe muscle weakness
  • low red blood cells (anemia)
  • bruises on the skin or bleeding
  • changes in eyesight
  • confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, or seizures (encephalitis)
  • swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis)

Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.

Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include:

  • chills or shaking
  • itching or rash
  • flushing
  • shortness of breath or wheezing
  • dizziness
  • fever
  • feel like passing out
  • back or neck pain
  • facial swelling

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment with LIBTAYO if you have severe side effects.

What is LIBTAYO?

LIBTAYO is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

It is not known if LIBTAYO is safe and effective in children.

Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you:

  • have immune system problems such as Crohn's disease, ulcerative colitis, or lupus
  • have had an organ transplant
  • have lung or breathing problems
  • have liver or kidney problems
  • have diabetes
  • are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby.
    Females who are able to become pregnant:
    • Your healthcare provider will give you a pregnancy test before you start treatment with LIBTAYO.
    • You should use an effective method of birth control during your treatment and for at least 4 months after the last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time.
    • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO.
  • are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive LIBTAYO?

  • Your healthcare provider will give you LIBTAYO into your vein through an intravenous (IV) line over 30 minutes.
  • LIBTAYO is usually given every 3 weeks.
  • Your healthcare provider will decide how many treatments you will need.
  • Your healthcare provider will do blood tests to check you for side effects.
  • If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

What are the possible side effects of LIBTAYO?

LIBTAYO can cause serious side effects, including:

  • See “What is the most important information I should know about LIBTAYO?”

The most common side effects of LIBTAYO include tiredness, rash and diarrhea.

These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of LIBTAYO.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about LIBTAYO, talk with your healthcare provider. You can ask your healthcare provider for information about LIBTAYO that is written for health professionals.

What are the ingredients of LIBTAYO?

Active ingredient: cemiplimab-rwlc

Inactive ingredients: L-histidine, L-histidine monohydrochloride monohydrate, sucrose, L-proline, Polysorbate 80, and Water for Injection, USP.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Side effects

The following serious adverse reactions are described elsewhere in the labeling.

  • Severe and Fatal Immune-Mediated Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]

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 PRECAUTIONS 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. LIBTAYO 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 LIBTAYO in 163 patients with advanced CSCC (metastatic or locally advanced disease) in Study 1423 and Study 1540 [see Clinical Studies]. 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. LIBTAYO 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 LIBTAYO.

Table 2: Adverse Reactions in ≥ 10% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540

Adverse Reactions LIBTAYO
N=163
All Grades % Grade 3-4 %
Skin and Subcutaneous Tissue
Rash* 25 1.2
Pruritus† 15 0
Gastrointestinal
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 includes 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 (%)†
Chemistry
Increased aspartate aminotransferase 3
Increased INR 2
Hypoalbuminemia 1
Hematology
Lymphopenia 7
Anemia 2
Electrolytes
Hypophosphatemia 4
Hyponatremia 3
Hypercalcemia 1
† Percentages are based on the number of patients with at least 1 post-baseline value available for that parameter.

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 LIBTAYO 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.

Read the entire FDA prescribing information for Libtayo (Cemiplimab-rwlc Injection)

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