Consumer medicine information

Libtayo

Cemiplimab

BRAND INFORMATION

Brand name

Libtayo

Active ingredient

Cemiplimab

Schedule

SUMMARY CMI

LIBTAYO^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. What is Libtayo used for?

Libtayo contains the active ingredient cemiplimab. Libtayo is an anti-cancer medicine. Libtayo is used in adults to treat types of skin cancer called advanced cutaneous squamous cell carcinoma (CSCC), and locally advanced or metastatic basal cell carcinoma (BCC), after previously receiving treatment with a hedgehog pathway inhibitor. Libtayo is also used in adults to treat advanced non-small cell lung cancer (NSCLC). For more information, see Section 1. What is Libtayo used for? in the full CMI.

2. What should I know before I am given Libtayo?

Do not use if you have ever had an allergic reaction to Libtayo or any of the ingredients listed at the end of the CMI.

Check with your doctor if you have an autoimmune disease, have had an organ transplant, or you have received or plan to receive a bone marrow transplant using bone marrow from another person, or if you have lung or breathing problems, liver problems, kidney problems, diabetes, or any other medical conditions.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

If you are able to become pregnant, you must use an effective method of contraception to avoid becoming pregnant while you are being treated with Libtayo and for at least 4 months after the last dose.

Do not breast feed while you are being treated with Libtayo and for at least 4 months after the last dose. For more information, see Section 2. What should I know before I am given Libtayo? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Libtayo and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Libtayo given?

Libtayo will be given to you under the supervision of a doctor experienced in cancer treatment.
Libtayo is given as a drip into a vein (intravenous infusion). The infusion will last about 30 minutes.
Libtayo is usually given every 3 weeks.

More instructions can be found in Section 4. How is Libtayo given? in the full CMI.

5. What should I know while using Libtayo?

Driving or using machines	Libtayo has no or minor influence on your ability to drive and use machines. If you feel tired, do not drive or use machines until you feel better.
Looking after your medicine	It is unlikely that you will be asked to store Libtayo yourself. It will usually be stored in the pharmacy or on the ward.

For more information, see Section 5. What should I know while using Libtayo? in the full CMI.

6. Are there any side effects?

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Libtayo.

Serious side effects can include skin problems, lung problems, liver problems, symptoms of type 1 diabetes, kidney problems, infusion-related reactions and problems in other parts of the body. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

FULL CMI

LIBTAYO^®

Active ingredient: cemiplimab

Consumer Medicine Information (CMI)

This leaflet provides important information about using Libtayo. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Libtayo.

It is important that you keep the Patient Alert Card with you during and after treatment.

Where to find information in this leaflet:

1. What is Libtayo used for?
2. What should I know before I am given Libtayo?
3. What if I am taking other medicines?
4. How is Libtayo given?
5. What should I know while using Libtayo?
6. Are there any side effects?
7. Product details

1. What is Libtayo used for?

Libtayo contains the active ingredient cemiplimab.
Libtayo is an anti-cancer medicine.

Libtayo is used in adults to treat:

a type of skin cancer called advanced cutaneous squamous cell carcinoma (CSCC)
a type of skin cancer called advanced basal cell carcinoma (BCC) after previously receiving treatment with a hedgehog pathway inhibitor
a type of lung cancer called advanced non-small cell lung cancer (NSCLC).

Libtayo may be given in combination with chemotherapy for NSCLC. It is important that you also read the package leaflets for the specific chemotherapy you may be receiving. If you have any questions about these medicines, ask your doctor.

Libtayo works by helping your immune system fight your cancer.

2. What should I know before I am given Libtayo?

Warnings

You should not be given Libtayo if:

you are allergic to cemiplimab, or any of the ingredients listed at the end of this leaflet.

If you think you may be allergic, or you are not sure, talk to your doctor before you are given Libtayo.

Some of the symptoms of an allergic reaction may include:

shortness of breath, wheezing or difficulty breathing
swelling of the face, lips, tongue, or other parts of the body
rash, itching or hives on the skin.

If you are not sure whether you should be given this medicine, talk to your doctor.

Check with your doctor if you:

you have an autoimmune disease (a condition where the body attacks its own cells)
you have had an organ transplant, or you have received or plan to receive a bone marrow transplant using bone marrow from another person (allogeneic hematopoietic stem cell transplant)
you have lung or breathing problems
you have liver problems
you have kidney problems
you have diabetes
you have any other medical conditions.

If you have not told your doctor about any of the above, tell him or her before you start taking Libtayo.

If any of the above apply to you, or you are not sure, talk to your doctor or nurse before you are given Libtayo.

Libtayo can cause some serious side effects that you need to tell your doctor about immediately. These problems may happen anytime during treatment or even after your treatment has ended. You may have more than one side effect at the same time. These serious side effects include:

Skin problems
Lung problems (pneumonitis)
Gut problems (colitis)
Liver problems (hepatitis)
Hormone gland problems - especially thyroid, pituitary, adrenal glands and the pancreas
Type 1 diabetes
Kidney problems (nephritis and kidney failure)
Central nervous system problems (such as meningitis)
Muscle problems (inflammation of the muscles called myositis)
Infusion-related reactions
Problems in other parts of the body (see Side effects).

Look out for these side effects while you are receiving Libtayo. See additional information under Section 6. Are there any side effects? If you have any of these side effects, talk to your doctor immediately.

Your doctor may give you other medicines in order to stop more severe reactions and reduce your symptoms. Your doctor also may delay your next dose of Libtayo or stop your treatment.

Children and adolescents

Libtayo should not be used in children and adolescents below 18 years of age.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Libtayo can harm your unborn baby.

Tell your doctor immediately if you become pregnant while you are being treated with Libtayo.

If you are able to become pregnant, you must use an effective method of contraception to avoid becoming pregnant:

while you are being treated with Libtayo and
for at least 4 months after the last dose.

Talk to your doctor about the contraception methods that you must use during this time.

Breastfeeding

If you are breast feeding or plan to breast-feed, ask your doctor for advice before you are given this medicine.

Do not breast feed while you are being treated with Libtayo and for at least 4 months after the last dose.

It is not known if Libtayo passes into your breast milk.

3. What if I am taking other medicines?

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor, pharmacist or nurse if you are taking or have ever taken any of the following medicines:

a cancer medicine called idelalisib
medicines that make your immune system weak - examples include corticosteroids, such as prednisone. These medicines may interfere with the effect of Libtayo. However, once you are treated with Libtayo, your doctor may give you corticosteroids to reduce the side effects that you may have with Libtayo.

4. How is Libtayo given?

Libtayo will be given to you under the supervision of a doctor experienced in cancer treatment.

Libtayo is given as a drip into a vein (intravenous infusion).

The infusion will last about 30 minutes.

Libtayo is usually given every 3 weeks.

How much you will receive

The recommended dose of Libtayo is 350 mg.

Your doctor will decide how much Libtayo you will receive and how many treatments you will need.

Your doctor will test your blood for certain side effects during your treatment.

If you miss an appointment

Call your doctor as soon as possible to make another appointment.

It is very important that you do not miss a dose of this medicine.

If you stop receiving Libtayo

Do not stop treatment of Libtayo unless you have discussed this with your doctor.

This is because stopping your treatment may stop the effect of the medicine.

Patient Alert Card

The information in this Leaflet can be found in the Patient Alert Card you have been given by your doctor. It is important that you keep this Patient Alert Card and show it to your partner or caregivers.

If you have any questions about your treatment, ask your doctor.

5. What should I know while using Libtayo?

Driving or using machines

Libtayo has no or minor influence on your ability to drive and use machines.

If you feel tired, do not drive or use machines until you feel better.

Storage

It is unlikely that you will be asked to store Libtayo yourself. It will usually be stored in the pharmacy or on the ward.

Disposal

Do not store any unused portion of the infusion solution for re use.

Your doctor or nurse will dispose of any leftover Libtayo that is no longer needed.

6. Are there any side effects?

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Libtayo.

Libtayo may cause side effects that appear weeks or months after your last dose.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or nurse to answer any questions you may have.

Libtayo acts on your immune system and may cause inflammation in parts of your body. Inflammation may cause serious damage to your body and may need treatment or require you to stop treatment with Libtayo. Some inflammatory conditions may also lead to death.

Talk to your doctor before trying to treat any of your symptoms.

You may need periodic blood tests or other tests so that your doctor can check that your liver and kidneys are functioning as normal.

The following side effects have been reported in clinical trials of patients treated with cemiplimab alone and patients treated with cemiplimab in combination with chemotherapy.

Less serious side effects

Less serious side effects

What to do

Generalised signs and symptoms:

Fatigue (feeling tired)
Trouble sleeping

Signs and symptoms of skin problems:

rash, itching
patches of thick, scaly or crusty skin

Signs and symptoms of problems in other organ systems:

Muscle or bone pain
Diarrhoea
Weak muscles
Joint pain, swelling
Inflammation of the mouth
Eye redness, eye pain, blurred vision, light sensitivity
High blood pressure
Low red blood cells
Low white blood cells (neutrophils)*
Low platelets*

Signs and symptoms of urinary tract infection:

urge to urinate, urinating more often, or painful urination
Hair loss

Speak to your doctor if you have any of these less serious side effects.

*Laboratory results - some side effects observed with Libtayo may not have symptoms and may only be discovered through blood tests.

Serious side effects

Serious side effects

What to do

Signs and symptoms of skin problems:

widespread rash or itching
skin blistering
ulcers in mouth or other mucous membrane.

Signs and symptoms of lung problems:

shortness of breath
chest pain
new or worsening cough

Signs and symptoms of problems with your stomach or intestines:

frequent diarrhoea or more bowel movements than usual
stools that are black or tarry or have blood and mucous
severe stomach (abdomen) pain or tenderness
coeliac disease (characterized by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency).

Signs and symptoms of liver problems:

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

Signs and symptoms of hormone gland problems (especially the thyroid, pituitary, and adrenal glands):

headaches that will not go away or unusual headaches
fast heartbeat
increased sweating
feeling more cold or hot than usual
severe tiredness
dizziness or fainting
weight gain or weight loss
feeling more hungry or thirsty than usual
hair loss
constipation
your voice gets deeper
very low blood pressure
urinating more often than usual
nausea or vomiting
stomach (abdomen) pain
changes in mood or behaviour (such as decreased sex drive, being irritable or forgetful)

Signs and symptoms of blood sugar problems or diabetic ketoacidosis:

feeling more hungry or thirsty than usual
needing to urinate more often
weight loss
feeling tired or sick
stomach pain
fast and deep breathing
confusion
unusual sleepiness
a sweet smell to your breath, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat

Signs and symptoms of kidney problems:

change in the amount or colour of your urine
blood in your urine
swollen ankles
feeling less hungry than normal.

Signs and symptoms of infusion (IV) reactions:

shortness of breath or wheezing
chills, shaking or fever
itching or rash
flushing or swollen face
dizziness
nausea, vomiting or abdominal pain.

Signs and symptoms of problems in other organ systems:
Nervous system problems

headache or stiff neck
fever or chills
feeling tired or weak
vomiting
confusion, memory problems or feeling sleepy
fits (seizures)
seeing or hearing things that are not really there (hallucinations)
severe muscle weakness
tingling, numbness
weakness or burning pain in arms or legs
paralysis in the extremities

Muscle and joint problems

joint pain or swelling
muscle pain or weakness which could be associated with a rash (dermatomyositis) or stiffness

Eye problems

inflammation of the eye
changes in eyesight
eye pain or redness
sensitivity to light

Heart and circulatory problems

changes in heartbeat, heart beating fast, seeming to skip a beat or pounding sensation
chest pain
shortness of breath

Blood problems

fever or chills
fast heartbeat
chest pain
shortness of breath
pale skin, or yellowing of the skin and whites of the eyes
weakness and fatigue
fainting
dark urine
a feeling of abdominal fullness

Other

dryness in many parts of the body from mouth to eyes, nose, throat and the top layers of skin
bruises on the skin or bleeding, enlarged liver and/or spleen, lymph node enlargement

There are possible side effects of treatment with Libtayo in people who have received a transplant:

Rejection of a transplanted organ
rejection has been reported with PD-1 inhibitors. Your doctor should tell you what signs and symptoms you should report, depending on the type of organ transplant you had

If any of the following happen after you have been given Libtayo tell your doctor immediately. If you cannot reach your doctor you must seek immediate medical attention

The above list includes serious side effects that may require urgent medical attention or hospitalisation.

These are not all of the possible side effects of Libtayo. Call your doctor for advice about side effects.

Other side effects not listed above may also occur in some patients.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is only available with a doctor's prescription.

What Libtayo contains

Active ingredient (main ingredient)	One ml of concentrate contains 50 mg of cemiplimab. Each vial contains 350 mg cemiplimab in 7 ml of concentrate.
Other ingredients (inactive ingredients)	Histidine Histidine monohydrochloride monohydrate Proline Sucrose Polysorbate 80 Water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What Libtayo looks like

Libtayo concentrate for solution for infusion (sterile concentrate) is supplied as a clear to slightly opalescent, colourless to pale yellow sterile solution that may contain trace amounts of translucent to white particles.

Each carton contains 1 glass vial with 7 ml of concentrate.

LIBTAYO cemiplimab 350 mg concentrate for solution for infusion AUST R 320609.

Who distributes Libtayo

Libtayo is supplied in Australia by:

Medison Pharma Australia Pty Ltd
1 Bligh Street
Sydney NSW 2000
Australia
Phone:1800 566 020
Email: [email protected]
www.medisonpharma.com.au

Distributed in New Zealand by:

Maxx Pharma NZ Limited
Level 4, 21 Queen Street
Auckland 1010
Toll Free Number (medical information): 0800 437 202
Email: [email protected]

This leaflet was prepared in October 2024.

lib-ccdsv10-cmiv10-25Oct2024

Published by MIMS December 2024

BRAND INFORMATION

Brand name

Libtayo

Active ingredient

Cemiplimab

Schedule

1 Name of Medicine

Libtayo 350 mg concentrate for solution for infusion.

2 Qualitative and Quantitative Composition

One mL of concentrate contains 50 mg of cemiplimab.
Each vial contains 350 mg of cemiplimab in 7 mL of solution.
Cemiplimab is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Concentrate for solution for infusion (sterile concentrate).
Clear to slightly opalescent, colourless to pale yellow solution with a pH of 6.0 and osmolality between 300 and 360 mmol/kg. The solution may contain trace amounts of translucent to white particles in a single-use vial.

4 Clinical Particulars

4.1 Therapeutic Indications

Cutaneous squamous cell carcinoma.

Libtayo as monotherapy is indicated for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (mCSCC or laCSCC) who are not candidates for curative surgery or curative radiation.

Non-small cell lung cancer.

Libtayo as monotherapy is indicated for the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) expressing PD-L1 tumour proportion score (TPS) ≥ 50% as determined by a validated test, with no EGFR, ALK or ROS1 aberrations, who have: locally advanced NSCLC and who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC.
Libtayo in combination with platinum‐based chemotherapy is indicated for the first‐line treatment of patients with NSCLC whose tumours have no EGFR, ALK or ROS1 aberrations and is: locally advanced where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

Basal cell carcinoma.

Libtayo as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.

4.2 Dose and Method of Administration

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.

Patient selection for NSCLC.

Select patients for treatment with cemiplimab based on PD-L1 expression confirmed by a validated test in locally advanced or metastatic NSCLC (see Section 5.1).

Posology.

Recommended dose.

The recommended dose is 350 mg cemiplimab every 3 weeks (Q3W) administered as an intravenous infusion over 30 minutes. Treatment may be continued until disease progression or unacceptable toxicity.

Dose modifications.

No dose reductions are recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability. Recommended modifications to manage adverse reactions are provided in Table 1.
Detailed guidelines for the management of immune-related adverse reactions are described in Table 1 (also see Section 4.4; Section 4.8).

Patient alert card.

All prescribers of Libtayo should be familiar with the educational materials and inform the patients about the Patient Alert Card explaining what to do should they experience any symptom of immune-related adverse reactions and infusion-related reactions. The physician will provide the Patient Alert Card to each patient.

Special populations.

Paediatric population.

The safety and efficacy of Libtayo in children and adolescents below the age of 18 years have not been established. No data are available.

Elderly.

No dose adjustment is recommended for elderly patients. Cemiplimab exposure is similar across all age groups (see Section 5.1; Section 5.2).

Renal impairment.

No dose adjustment of Libtayo is recommended for patients with renal impairment. There are limited data for Libtayo in patients with severe renal impairment CL_cr 15 to 29 mL/min (see Section 5.2).

Hepatic impairment.

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Libtayo has not been studied in patients with severe hepatic impairment. There are insufficient data in patients with severe hepatic impairment for dosing recommendations (see Section 5.2).

Method of administration.

Libtayo is for intravenous use. It is administered by intravenous infusion over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding, in-line or add-on filter (0.2 micron to 5 micron pore size).
Other medicinal products should not be co-administered through the same infusion line.
For instructions on dilution of the medicinal product before administration, see Section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.

4.4 Special Warnings and Precautions for Use

Traceability.

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Immune-mediated adverse reactions.

Severe and fatal immune-mediated adverse reactions have been observed with cemiplimab (see Section 4.2; Section 4.8). These immune-mediated reactions may involve any organ system. Immune-mediated reactions can manifest at any time during treatment with cemiplimab; however, immune-mediated adverse reactions can occur after discontinuation of cemiplimab.
The guidance for immune-mediated adverse reactions applies to Libtayo monotherapy and in combination with chemotherapy.
Immune-mediated adverse reactions affecting more than one body system can occur simultaneously, such as myositis and myocarditis or myasthenia gravis, in patients treated with cemiplimab or other PD-1/PD-L1 inhibitors.
Monitor patients for signs and symptoms of immune-mediated adverse reactions. Immune-mediated adverse reactions should be managed with cemiplimab treatment modifications, hormone replacement therapy (if clinically indicated), and corticosteroids. For suspected immune-mediated adverse reactions, patients should be evaluated to confirm an immune-mediated adverse reaction and to exclude other possible causes, including infection. Depending upon the severity of the adverse reaction, cemiplimab should be withheld or permanently discontinued (see Section 4.2).
Immune-mediated pneumonitis. Immune-mediated pneumonitis, defined as requiring use of corticosteroids with no clear alternate aetiology, including fatal cases, has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for signs and symptoms of pneumonitis and causes other than immune-mediated pneumonitis should be ruled out. Patients with suspected pneumonitis should be evaluated with radiographic imaging as indicated based on clinical evaluation and managed with cemiplimab treatment modifications and corticosteroids (see Section 4.2).
Immune-mediated colitis. Immune-mediated diarrhoea or colitis, defined as requiring use of corticosteroids with no clear alternate aetiology, has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for signs and symptoms of diarrhoea or colitis and managed with cemiplimab treatment modifications, anti-diarrhoeal agents, and corticosteroids (see Section 4.2).
Immune-mediated hepatitis. Immune-mediated hepatitis, defined as requiring use of corticosteroids with no clear alternate aetiology, including fatal cases, has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for abnormal liver tests prior to and periodically during treatment as indicated based on clinical evaluation and managed with cemiplimab treatment modifications and corticosteroids (see Section 4.2).
Immune-mediated endocrinopathies. Immune-mediated endocrinopathies, defined as treatment-emergent endocrinopathies with no clear alternate aetiology, have been observed in patients receiving cemiplimab (see Section 4.8).

Thyroid disorders (hypothyroidism/hyperthyroidism/thyroiditis).

Thyroid disorders have been observed in patients receiving cemiplimab. Thyroiditis can present with or without an alteration in thyroid function tests. Hypothyroidism can follow hyperthyroidism. Thyroid disorders can occur at any time during the treatment. Patients should be monitored for changes in thyroid function at the start of treatment and periodically during the treatment as indicated based on clinical evaluation (see Section 4.8). Patients should be managed with hormone replacement therapy (if indicated) and cemiplimab treatment modifications. Hyperthyroidism should be managed according to standard medical practice (see Section 4.2).

Hypophysitis.

Hypophysitis has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for signs and symptoms of hypophysitis and managed with cemiplimab treatment modifications, corticosteroids and hormone replacement, as clinically indicated (see Section 4.2).

Adrenal insufficiency.

Adrenal insufficiency has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for signs and symptoms of adrenal insufficiency during and after treatment and managed with cemiplimab treatment modifications, corticosteroids and hormone replacement, as clinically indicated (see Section 4.2).

Type 1 diabetes mellitus.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has been observed in patients receiving cemiplimab (see Section 4.8). Patients should be monitored for hyperglycaemia and signs and symptoms of diabetes as indicated based on clinical evaluation and managed with oral anti-hyperglycaemics or insulin and cemiplimab treatment modifications (see Section 4.2).
Immune-mediated skin adverse reactions. Immune-mediated skin adverse reactions, defined as requiring use of systemic corticosteroids with no clear alternate aetiology, including severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (some cases with fatal outcome), and other skin reactions such as rash, erythema multiforme, pemphigoid, have been reported in association with cemiplimab treatment (see Section 4.8).
Patients should be monitored for evidence of suspected severe skin reactions and exclude other causes. Patients should be managed with cemiplimab treatment modifications and corticosteroids (see Section 4.2). For symptoms or signs of SJS or TEN, refer the patient for specialised care for assessment and treatment and manage patient with treatment modifications (see Section 4.2).
Cases of SJS, fatal TEN and stomatitis occurred following 1 dose of cemiplimab in patients with prior exposure to idelalisib, who were participating in a clinical trial evaluating cemiplimab in Non-Hodgkin Lymphoma (NHL), and who had recent exposure to sulfa containing antibiotics (see Section 4.8). Patients should be managed with cemiplimab treatment modifications and corticosteroids as described above (see Section 4.2). For symptoms or signs of SJS or TEN, refer the patient for specialised care for assessment and treatment and manage patient with treatment modifications (see Section 4.2).
Immune-mediated nephritis. Immune-mediated nephritis, defined as requiring use of corticosteroids with no clear alternate aetiology, including a fatal case, has been observed in patients receiving cemiplimab (see Section 4.8). Monitor patients for changes in renal function. Patients should be managed with cemiplimab treatment modifications and corticosteroids (see Section 4.2).

Other immune-mediated adverse reactions.

Other fatal and life-threatening immune-mediated adverse reactions have been observed in patients receiving cemiplimab including paraneoplastic encephalomyelitis meningitis, myositis and myocarditis (see Section 4.8 for other immune-related adverse reactions).
Evaluate suspected immune-mediated adverse reactions to exclude other causes. Patients should be monitored for signs and symptoms of immune-mediated adverse reactions and managed with cemiplimab treatment modifications and corticosteroids as clinically indicated (see Section 4.2; Section 4.8).
Cases of solid organ transplant rejection have been reported in the post-marketing setting with cemiplimab and other PD-1/PD-L1 inhibitors. Cases of graft-versus-host disease have been reported in the post-marketing setting in patients treated with other PD-1/PD-L1 inhibitors in association with allogeneic hematopoietic stem cell transplant.
Haemophagocytic lymphohistiocytosis (HLH) has been reported in the postmarketing setting with Libtayo (see Section 4.8). Patients should be monitored for clinical signs and symptoms of HLH. If HLH is suspected, administration of Libtayo should be withheld and treatment initiated (see Section 4.2). If HLH is confirmed, administration of Libtayo should be permanently discontinued.

Infusion-related reactions.

Cemiplimab can cause severe or life-threatening infusion-related reactions (see Section 4.8). Patients should be monitored for signs and symptoms of infusion-related reactions and managed with cemiplimab treatment modifications and corticosteroids. Cemiplimab should be interrupted or the rate of infusion slowed for mild or moderate infusion-related reactions. The infusion should be stopped and cemiplimab should be permanently discontinued for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions (see Section 4.2).

Patients excluded from clinical studies.

Patients that had active infections or that were immunocompromised were not included in the main study. For a full list of patients excluded from clinical trials, see Section 5.1.
In the absence of data, cemiplimab should be used with caution in these populations after careful evaluation of the balance of benefits and risks for the patient.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No pharmacokinetic (PK) drug-drug interaction studies have been conducted with cemiplimab.
The use of systemic corticosteroids or immunosuppressants before starting cemiplimab, except for physiological doses of systemic corticosteroid (≤ 10 mg/day prednisone or equivalent), should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of cemiplimab. However, systemic corticosteroids or other immunosuppressants can be used after starting cemiplimab to treat immune-related adverse reactions (see Section 4.2).

4.6 Fertility, Pregnancy and Lactation

Women of childbearing potential.

Women of childbearing potential should use effective contraception during treatment with cemiplimab and for at least 4 months after the last dose of cemiplimab.

Effects on fertility.

No clinical data are available on the possible effects of cemiplimab on fertility. No effects on fertility assessment parameters (menstrual cycle and semen analysis) or male and female reproductive organs were observed in a 3-month repeat dose fertility assessment study with sexually mature cynomolgus monkeys at doses up to the highest dose studied of 50 mg/kg/week IV, resulting in exposures (AUC and C_max) approximately 20 times that expected in patients.
(Category D)
Animal reproduction studies have not been conducted with cemiplimab. There are no available data on the use of cemiplimab in pregnant women. As reported in the literature, PD-1/PD-L1 signalling pathway plays a role in sustaining pregnancy by maintaining immunological tolerance and animal studies have shown that PD-1 receptor blockade can result in an increase in foetal loss.
The increase of spontaneous abortion and/or resorption in animals with restricted PD-L1 expression (knock-out or anti-PD1/PD-L1 monoclonal antibodies) has been shown in both mice and monkeys. These animal species have similar maternal foetal interface to that in humans.
Human IgG4 is known to cross the placental barrier and cemiplimab is an IgG4; therefore, cemiplimab has the potential to be transmitted from the mother to the developing foetus. Cemiplimab is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.
It is unknown whether cemiplimab is secreted in human milk. It is known that antibodies (including IgG4) are secreted in human milk; a risk to the breastfeeding newborn/infant cannot be excluded.
If a woman chooses to be treated with cemiplimab, she should be instructed not to breastfeed while being treated with cemiplimab and for at least 4 months after the last dose.

4.7 Effects on Ability to Drive and Use Machines

Cemiplimab has no or negligible influence on the ability to drive and use machines. Fatigue has been reported following treatment with cemiplimab (see Section 4.8).

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Immune-mediated adverse reactions can occur with cemiplimab. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of cemiplimab (see Description of selected adverse reactions).

Libtayo as monotherapy.

The safety of cemiplimab monotherapy has been evaluated in 1281 patients with advanced solid malignancies who received cemiplimab in 5 clinical studies. These studies included 384 patients with advanced CSCC, 138 patients with advanced BCC, 355 patients with advanced NSCLC, 300 patients with recurrent or metastatic cervical cancer and 104 patients with other solid tumours. The median duration of exposure to cemiplimab was 27 weeks (range: 2 days to 144 weeks). Among the 1281 patients, 53% were exposed for ≥ 6 months and 26% were exposed for ≥ 12 months.
Immune-mediated adverse reactions occurred in 20.8% of patients treated with cemiplimab in clinical trials including Grade 5 (0.3%), Grade 4 (0.6%), Grade 3 (5.7%) and Grade 2 (11.2%). Immune-mediated adverse reactions led to permanent discontinuation of cemiplimab in 4.6% of patients. The most common immune-mediated adverse reactions were hypothyroidism (6.8%), hyperthyroidism (3.0%), immune-mediated pneumonitis (2.6%), immune-mediated hepatitis (2.4%), immune-mediated colitis (2.0%) and immune-mediated skin adverse reactions (1.9%) (see Description of selected adverse reactions; see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration for recommended treatment modifications).
Adverse events were serious in 32.4% of patients.
Adverse events led to permanent discontinuation of cemiplimab in 9.4% of patients.
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in association with cemiplimab treatment (see Section 4.4).

Tabulated list of adverse reactions.

Listed in Table 2 are adverse reactions by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Libtayo in combination with platinum‐based chemotherapy.

The safety of Libtayo in combination with platinum‐based chemotherapy has been evaluated in a clinical study of 465 patients with locally advanced or metastatic NSCLC. The median duration of exposure was 38.5 weeks (range: 10 days to 102.6 weeks) in the Libtayo and chemotherapy group, and 21.3 weeks (range: 4 days to 95 weeks) in the chemotherapy group.
The safety population characteristics were: median age of 63 years (range: 25 to 82 years), 268 (85.9%) male, 267 (85.6%) White, ECOG PS of 0 in 51 patients (16.3%) and 1 in 259 patients (83%).
Immune‑mediated adverse reactions occurred in 18.9% of patients including Grade 5 (0.3%), Grade 3 (2.6%), and Grade 2 (7.4%). Immune-mediated adverse reactions led to permanent discontinuation of cemiplimab in 1.0% of patients. The most common immune-mediated adverse reactions were hypothyroidism (7.7%), hyperthyroidism (5.1%), increased blood thyroid stimulating hormone (4.2%), immune-mediated skin reaction (1.9%), immune-mediated pneumonitis (1.9%), and decreased blood thyroid stimulating hormone (1.6%) (see Description of selected adverse reactions; see Section 4.8; Section 4.2).
Adverse events were serious in 25.3% of patients.
Adverse events led to permanent discontinuation of cemiplimab in 5.1% of patients.
Table 3 summarises the incidence of adverse reactions that occurred in patients receiving Libtayo in combination with chemotherapy in Study 16113.

Description of selected adverse reactions.

The selected adverse reactions described below are based on safety of cemiplimab monotherapy in 1281 patients with advanced solid malignancies in five clinical studies.
These selected adverse reactions were consistent when Libtayo was administered in monotherapy or in combination with chemotherapy.
Immune-mediated adverse reactions (see Section 4.2; Section 4.4).

Immune-mediated pneumonitis.

Immune-mediated pneumonitis occurred in 33 (2.6%) of 1281 patients receiving cemiplimab, including 4 (0.3%) patients with Grade 4, 8 (0.6%) patients with Grade 3 pneumonitis. Immune-mediated pneumonitis led to permanent discontinuation of cemiplimab in 17 (1.3%) of 1281 patients. Among the 33 patients with immune-mediated pneumonitis, the median time to onset was 2.7 months (range: 7 days to 22.2 months) and the median duration of pneumonitis was 1.1 months (range: 5 days to 16.9 months). Twenty-seven of the 33 patients (81.8%) received high-dose corticosteroids for a median of 15 days (range: 1 day to 5.9 months). Resolution of pneumonitis had occurred in 20 (60.6%) of the 33 patients at the time of data cut-off.

Immune-mediated colitis.

Immune-mediated diarrhoea or colitis occurred in 25 (2.0%) of 1281 patients receiving cemiplimab including 10 (0.8%) with Grade 3 immune-mediated diarrhoea or colitis. Immune-mediated diarrhoea or colitis led to permanent discontinuation of cemiplimab in 5 (0.4%) of 1281 patients. Among the 25 patients with immune-mediated diarrhoea or colitis, the median time to onset was 3.8 months (range: 1 day to 16.6 months) and the median duration of immune-mediated diarrhoea or colitis was 2.1 months (range: 4 days to 26.8 months). Nineteen patients (76.0%) with immune-mediated diarrhoea or colitis received high-dose corticosteroids for a median of 22 days (range: 2 days to 5.2 months). Resolution of immune-mediated diarrhoea or colitis had occurred in 14 (56%) of the 25 patients at the time of data cut-off.

Immune-mediated hepatitis.

Immune-mediated hepatitis occurred in 31 (2.4%) of 1281 patients receiving cemiplimab including 1 (< 0.1%) patient with Grade 5, 4 (0.3%) patients with Grade 4, and 21 (1.6%) patients with Grade 3 immune-mediated hepatitis. Immune-mediated hepatitis led to permanent discontinuation of cemiplimab in 18 (1.4%) of 1281 patients. Among the 31 patients with immune-mediated hepatitis, the median time to onset was 2.8 months (range: 7 days to 22.5 months) and the median duration of hepatitis was 2.3 months (range: 5 days to 8.7 months). Twenty-seven (87.1%) patients with immune-mediated hepatitis received high-dose corticosteroids for a median of 24 days (range: 2 days to 3.8 months). Resolution of hepatitis had occurred in 12 (38.7%) of the 31 patients at the time of data cut-off.

Immune-mediated endocrinopathies.

Hypothyroidism occurred in 87 (6.8%) of 1281 patients receiving cemiplimab including 1 (< 0.1%) patient with Grade 3 hypothyroidism. Three (0.2%) of 1281 patients discontinued cemiplimab due to hypothyroidism. Among the 87 patients with hypothyroidism, the median time to onset was 4.0 months (range: 15 days to 18.9 months) with a median duration of 9.2 months (range: 1 day to 37.1 months). Resolution of hypothyroidism had occurred in 5 (5.7%) of the 87 patients at the time of data cutoff.
Hyperthyroidism occurred in 39 (3.0%) of 1281 patients receiving cemiplimab including 1 (< 0.1%) patient with Grade 3 and 11 (0.9%) patients with Grade 2 hyperthyroidism. No patient discontinued cemiplimab due to hyperthyroidism. Among the 39 patients with hyperthyroidism, the median time to onset was 1.9 months (range: 20 days to 23.8 months) and the median duration was 1.9 months (range: 9 days to 32.7 months). Resolution of hyperthyroidism had occurred in 22 (56.4%) of the 39 patients at the time of data cutoff.
Thyroiditis occurred in 8 (0.6%) of 1281 patients receiving cemiplimab including 4 (0.3%) patients with Grade 2 thyroiditis. No patient discontinued cemiplimab due to thyroiditis. Resolution of thyroiditis had occurred in 1 (16.7 12.5%) of the 68 patients at the time of data cutoff.
Adrenal insufficiency occurred in 6 (0.5%) of 1281 patients receiving cemiplimab including 6 (0.5%) patients with Grade 3 adrenal insufficiency. One (< 0.1%) of 1281 patients discontinued cemiplimab due to adrenal insufficiency. Among the 6 patients with adrenal insufficiency, the median time to onset was 7.5 months (range: 4.2 months to 18.3 months) and the median duration was 2.9 months (range: 22 days to 6.1 months). Five of the 6 patients (83.3%) were treated with systemic corticosteroids. Adrenal insufficiency resolved in 1 of the 6 patients (16.7%) at the time of data cutoff.
Hypophysitis occurred in 7 (0.5%) of 1281 patients receiving cemiplimab, including 3 (0.2%) patients with Grade 3 hypophysitis. One (< 0.1%) of 1281 patients discontinued cemiplimab due to hypophysitis. Among the 7 patients with hypophysitis, the median time to onset was 7.4 months (range: 2.5 months to 10.4 months) with a median duration of 2.7 months (range: 9 days to 34.9 months). Six of the 7 patients (85.7%) were treated with corticosteroids. Hypophysitis resolved in 1 of the 7 patients (14.3%) at the time of data cutoff.
Type 1 diabetes mellitus without an alternative aetiology occurred in 1 (< 0.1%) of 1281 patients (Grade 4).

Immune-mediated skin adverse reactions.

Immune-mediated skin adverse reactions occurred in 24 (1.9%) of 1281 patients receiving cemiplimab including 11(0.9%) patients with Grade 3 immune-mediated skin adverse reactions. Immune-mediated skin adverse reactions led to permanent discontinuation of cemiplimab in 2 (0.2%) of 1281 patients. Among the 24 patients with immune-mediated skin adverse reactions, the median time to onset was 2.0 months (range: 2 days to 17.0 months) and the median duration was 2.9 months (range: 8 days to 38.8 months). Seventeen patients (70.8%) with immune-mediated skin adverse reactions received high-dose corticosteroids for a median of 10 days (range: 1 day to 2.9 months). Resolution had occurred in 17 (70.8%) of 24 patients at the time of data cut-off.

Immune-mediated nephritis.

Immune-mediated nephritis occurred in 9 (0.7%) of 1281 patients receiving cemiplimab including 1 (< 0.1%) patient with Grade 5, and 1 (< 0.1%) patient with Grade 3 immune-mediated nephritis. Immune-mediated led to permanent discontinuation of cemiplimab in 2 (0.2%) of 1281 patients. Among the 9 patients with immune-mediated nephritis, the median time to onset was 2.1 months (range: 14 days to 12.5 months) and the median duration of nephritis was 1.5 months (range: 9 days to 5.5 months). Six (66.7%) patients with immune-mediated nephritis received high-dose corticosteroids for a median of 18 days (range: 3 days to 1.3 months). Resolution of nephritis had occurred in 7 (77.8%) of the 9 patients at the time of data cut-off.

Other immune-mediated adverse reactions.

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% (unless otherwise noted) of 1281 patients with advanced solid malignancies treated with cemiplimab monotherapy in clinical trials. The events were Grade 3 or less unless stated otherwise:
Nervous system disorders: aseptic meningitis, paraneoplastic encephalomyelitis (Grade 5), chronic inflammatory demyelinating polyradiculoneuropathy, encephalitis, myasthenia gravis, peripheral neuropathy^a.
Cardiac disorders: myocarditis^b (Grade 5), pericarditis^c.
Immune system disorders: immune thrombocytopenia.
Musculoskeletal and connective tissue disorders: arthralgia (1.2%), arthritis^d, muscular weakness, myalgia, myositis^e(Grade 4), polymyalgia rheumatica, Sjogren's syndrome.
Skin and subcutaneous tissue disorders: pruritus.
Eye disorders: keratitis, uveitis^f (Grade 4).
Gastrointestinal disorders: stomatitis, immune-mediated gastritis.
^a Includes neuritis, peripheral neuropathy, peripheral sensory neuropathy, and polyneuropathy.
^b Includes autoimmune myocarditis, immune-mediated myocarditis, and myocarditis.
^c Includes autoimmune pericarditis and pericarditis.
^d Includes arthritis, immune-mediated arthritis, and polyarthritis.
^e Includes myositis and dermatomyositis.
^f Reported in clinical studies outside the pooled safety dataset.
The following additional immune-mediated adverse reactions were observed in patients receiving combination therapy in clinical trials: vasculitis, Guillain-Barre syndrome, central nervous system inflammation, and meningitis (Grade 4), each with the frequency of rare (≥ 1/10,000 to < 1/1,000).
Immune checkpoint inhibitor class effects. There have been cases of the following adverse reactions reported during treatment with other immune checkpoint inhibitors, which might also occur during treatment with cemiplimab: coeliac disease and pancreatic exocrine insufficiency.
Infusion-related reactions. Infusion-related reactions occurred in 94 (7.3%) of 1281 patients treated with cemiplimab including 2 (0.2%) patients with Grade 3 or 4 infusion-related reaction. Common symptoms of infusion-related reaction include nausea, pyrexia, and vomiting.

Immunogenicity.

As with all therapeutic proteins, there is a potential for immunogenicity with cemiplimab. Approximately 2.1% of patients developed treatment-emergent antibodies to cemiplimab, with approximately 0.3% of patients exhibiting persistent antibody responses. No neutralising antibodies have been observed. There was no evidence of an altered PK or safety profile with anti-cemiplimab antibody development. Immunogenicity data are highly dependent on the sensitivity and specificity of the assay as well as other factors. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to cemiplimab with the incidence of antibodies to other products may be misleading.

Postmarketing experience.

The following adverse reactions have been reported during post-approval use of Libtayo. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (see Section 4.4 Special Warnings and Precautions for Use).

Immune system disorder.

Solid organ transplant rejection, autoimmune haemolytic anaemia.

Blood and lymphatic system disorders.

Haemophagocytic lymphohistiocytosis (HLH).

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
For general advice on overdose management, contact the Poisons Information Centre at telephone number 13 11 26.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antineoplastic agents, PD-1/PD-L1 (programmed cell death protein 1/death ligand 1) inhibitors. ATC code: L01FF06.

Mechanism of action.

Cemiplimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with its ligands PD-L1 and PD-L2. Engagement of PD-1 with its ligands PD-L1 and PD-L2, which are expressed by antigen presenting cells and may be expressed by tumour cells and/or other cells in the tumour microenvironment, results in inhibition of T cell function such as proliferation, cytokine secretion, and cytotoxic activity. Cemiplimab potentiates T cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2 ligands.

Clinical efficacy.

CSCC. The efficacy and safety of cemiplimab in patients with mCSCC (nodal or distant) or laCSCC who were not candidates for curative surgery or curative radiation were studied in clinical trial R2810-ONC-1540 (Study 1540). Study 1540 was a phase 2, open label, multi-centre study that enrolled 193 advanced CSCC patients in groups 1 to 3:59 patients with mCSCC treated with cemiplimab 3 mg/kg Q2W (group 1), 78 patients with laCSCC treated with cemiplimab 3 mg/kg Q2W (group 2), 56 patients with mCSCC treated with cemiplimab 350 mg Q3W (group 3).
Patients with any of the following were excluded: autoimmune disease that required systemic therapy with immunosuppressant agents within 5 years; history of solid organ transplant; history of pneumonitis within the last 5 years; prior treatment with anti PD-1/PD-L1 or other immune checkpoint inhibitor therapy; active infection requiring therapy, including known infection with human immunodeficiency virus, or active infection with hepatitis B or hepatitis C virus; chronic lymphocytic leukaemia (CLL); brain metastases or Eastern Cooperative Oncology Group (ECOG) performance score (PS) ≥ 2.
In Study 1540, patients received cemiplimab until progression of disease, unacceptable toxicity or completion of planned treatment (3 mg/kg Q2W for 96 weeks (groups 1 and 2) or 350 mg Q3W for 54 weeks group 3). If patients with locally advanced disease showed sufficient response to treatment, surgery with curative intent was permitted. Tumour response assessments were performed every 8 or 9 weeks (for patients receiving 3 mg/kg Q2W or 350 mg Q3W, respectively). The primary endpoint of Study 1540 was confirmed objective response rate (ORR), as assessed by independent central review (ICR). For patients with mCSCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1). For patients with externally visible target lesions (laCSCC and mCSCC), ORR was determined by a composite endpoint that integrated ICR assessments of radiologic data (RECIST 1.1) and digital medical photography (WHO criteria). The key secondary endpoint was duration of response (DOR) by ICR. Other secondary endpoints included ORR and DOR by investigator assessment (IA), progression free survival (PFS) by ICR and IA, overall survival (OS), complete response rate (CR) by ICR, and change in scores in patient reported outcomes on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30).
The efficacy analysis presents results from 193 advanced CSCC patients in study 1540 groups 1 to 3. Of these 193 patients, 115 had mCSCC (nodal or distant) and 78 had laCSCC. The median age was 72 years (range: 38 to 96): seventy-eight (40.4%) patients were 75 years or older, 66 patients (34.2%) were 65 to less than 75 years, and 49 patients (25.4%) were less than 65 years. A total of 161 (83.4%) patients were male, and 187 (96.9%) patients were White; the ECOG PS was 0 in 86 patients (44.6%) and 1 in 107 patients (55.4%). Sixty-five (33.7%) of patients had received at least 1 prior anti-cancer systemic therapy, 157 (81.3%) patients had received prior cancer-related surgery, and 113 (67.9%) patients had received prior radiotherapy. Among patients with mCSCC, 88 (76.5%) had distant metastases, and 26 (22.6%) had only nodal metastases.
At the time of primary analysis, median duration of follow-up was 7.9 months, 9.3 months, and 8.1 months for groups 1, 2, and 3, respectively. The CR rate and ORR for group 1 were 6.8% and 47.5%, respectively. The CR rate and ORR for group 2 were 12.8% and 43.6%, respectively. The CR rate and ORR for group 3 were 5.4% and 41.1%, respectively.
Efficacy results based on the final analysis for study 1540 groups 1 to 3 are presented in Table 4.
In the final analysis, with median duration of follow-up of 18.5 months, 15.5 months, and 17.3 months for groups 1, 2, and 3, respectively, complete response rate increases over time for mCSCC patients (3 mg/kg Q2W and 350 mg Q3W groups). As for the primary analysis, similar ORR were reported in the final analysis across groups 1 to 3.
Efficacy results based on the final analysis for study 1540 groups 1 to 3 are presented in Table 4 and Figure 1.

Efficacy and PD-L1 status.

Clinical activity was observed regardless of tumour PD-L1 expression status.
NSCLC.

First-line treatment of NSCLC with Libtayo as monotherapy.

The efficacy and safety of cemiplimab in patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation, with locally advanced NSCLC who have progressed after treatment with chemoradiation, or with metastatic NSCLC were evaluated in Study 1624, a randomised, open-label, multi-centre study.
The study was designed to enrol patients with tumour PD-L1 expression ≥ 50%. A total of 710 patients (Intent-To-Treat [ITT] population) were enrolled, and an analysis was performed on the pre-specified population (n=563) who had PD-L1 expression ≥ 50% using the PD-L1 IHC 22C3 pharmDx assay according to its labelling.
The study excluded patients with EGFR, ALK or ROS1 genomic tumour aberrations, medical conditions that required systemic immunosuppression, uncontrolled infection with hepatitis B (HBV) or hepatitis C (HCV) or human immunodeficiency virus (HIV), or autoimmune disease that required systemic therapy within 2 years of treatment. Patients with type 1 diabetes mellitus or hypothyroidism only requiring hormone replacement were eligible. The study included patients who had not received prior systemic therapy for recurrent or metastatic NSCLC. Treatment of brain metastases was permitted, and patients could be enrolled if they had been adequately treated and had neurologically returned to baseline for at least 2 weeks prior to randomisation. Radiological confirmation of stability or response was not required.
Randomisation was stratified by histology (non-squamous vs squamous). Patients were randomised (1:1) to receive cemiplimab 350 mg intravenously (IV) every 3 weeks for up to 108 weeks or investigator's choice of the following platinum-doublet chemotherapy regimens for 4 to 6 cycles:
Paclitaxel + cisplatin or carboplatin;
Gemcitabine + cisplatin or carboplatin;
Pemetrexed + cisplatin or carboplatin followed by optional pemetrexed maintenance (This regimen was not recommended for patients with squamous NSCLC).
Treatment with cemiplimab continued until RECIST 1.1-defined progressive disease, unacceptable toxicity, or up to 108 weeks. Patients who experienced IRC-assessed RECIST 1.1-defined progressive disease on cemiplimab therapy were permitted to continue treatment with cemiplimab with an addition of 4 cycles of histology-specific chemotherapy until further progression was observed. Patients who experienced IRC-assessed RECIST 1.1-defined progressive disease on chemotherapy treatment were permitted to receive cemiplimab treatment until further progression, unacceptable toxicity or up to 108 weeks. Of the 203 patients randomised to receive chemotherapy who had IRC-assessed RECIST 1.1-defined disease progression, 150 (73.9%) patients crossed over to treatment with cemiplimab.
Assessment of tumour status was performed every 9 weeks. The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS). An additional efficacy endpoint was objective response rate (ORR).
The study population characteristics of patients in the ITT population are included in Table 5.

In the pre-specified population with PD-L1 ≥ 50%, baseline patient and disease characteristics were consistent with those in the ITT population.
The study demonstrated statistically significant improvement in OS and PFS for patients randomised to cemiplimab as compared with chemotherapy. In the ITT population, the median duration of response was 21 months (range: 1.9 - 23.3 months) in the cemiplimab group and 6 months (range 1.3 - 16.5 months) in the chemotherapy group. Median duration of follow-up was 13.1 months in the cemiplimab group and 13.1 months in the chemotherapy group.
Efficacy results for the ITT and the pre-specified population with PD-L1 ≥ 50% are presented in Table 6, and Figure 2, Figure 3, Figure 4, and Figure 5.

First-line treatment of NSCLC with Libtayo in combination with platinum-based chemotherapy.

The efficacy and safety of Libtayo in combination with platinum-based chemotherapy was evaluated in Study 16113, a randomised, multi-centre, double-blind, active-controlled trial in 466 patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation, or with metastatic NSCLC, regardless of tumour PD-L1 expression status and who had not previously received systemic treatment for metastatic NSCLC.
Patients with EGFR, ALK or ROS1 genomic tumour aberrations; a medical condition that required systemic immunosuppression, active infection with hepatitis B (HBV) or hepatitis C (HCV), uncontrolled human immunodeficiency disease (HIV), or ongoing or recent autoimmune disease that required systemic therapy were ineligible. Patients with a history of brain metastases were eligible if they had been adequately treated and had neurologically returned to baseline for at least 2 weeks prior to randomisation. Radiological confirmation of stability or response was not required.
Randomisation was stratified by histology (non-squamous vs squamous) and PD-L1 expression (< 1% versus 1% to 49% versus ≥ 50%) according to the VENTANA PD-L1 (SP263) assay. Patients were randomised (2:1) to receive either Libtayo 350 mg intravenously (IV) every 3 weeks for 108 weeks plus platinum-based chemotherapy every 3 weeks for 4 cycles or placebo intravenously (IV) every 3 weeks for 108 weeks plus platinum-based chemotherapy every 3 weeks for 4 cycles.
Treatment with Libtayo and chemotherapy or placebo and chemotherapy continued until RECIST 1.1-defined progressive disease, unacceptable toxicity, or 108 weeks. Assessment of tumour status was performed every 9 weeks beginning at week 9 during year 1 and every 12 weeks beginning at week 55 during year 2. The primary efficacy endpoint was overall survival (OS). Additional efficacy endpoints were progression-free survival (PFS) and objective response rate (ORR).
The study population characteristics were: median age of 63 years (25 to 82 years), 41% age 65 or older; 85.9% male; 85.6% White, 14.4% Asian; an ECOG PS 0 and 1 in 16.3% and 83% respectively; 85.6% had metastatic disease and 14.4% had stage IIIB or IIIC disease and were not candidates for surgical resection or definitive chemoradiation per investigator assessment; 57.4% had non-squamous and 42.6% had squamous histology; and 7.7% had history of treated brain metastases at baseline.
For the primary analysis (Table 7), the median duration of follow up for cemiplimab and chemotherapy arm was 16.3 months, and 16.7 months for placebo and chemotherapy arm. The overall median duration of exposure was 38.45 weeks (range: 1.4 to 102.6 weeks) for cemiplimab/chemotherapy and 21.30 weeks (range: 0.6 to 95.0 weeks) for placebo/chemotherapy. At the time of data cut off, 224 (71.8%) patients had been treated with cemiplimab for ≥ 24 weeks and 119 (38.1%) patients have been treated for ≥ 48 weeks.
The study demonstrated a statistically significant improvement in OS for patients randomised to Libtayo in combination with chemotherapy compared with placebo in combination with chemotherapy.
Efficacy results are presented in Table 7 and Figure 6.

In a subgroup analysis relative to chemotherapy, OS benefit was shown in patients treated with Libtayo in combination with chemotherapy with squamous histology (median OS 21.9 in the cemiplimab plus chemotherapy group vs. 13.8 in the chemotherapy group, HR [95% CI] 0.557 [0.370, 0.840], n=200) and in patients with non-squamous histology (median OS 15.8 in the cemiplimab plus chemotherapy group vs. 13.0 in the chemotherapy group, HR [95% CI] 0.785 [0.539, 1.143], n=266).

Efficacy and PD-L1 status.

Efficacy by PD-L1 status is shown in Table 8. See Table 9.

BCC. The efficacy and safety of cemiplimab in patients with advanced basal cell carcinoma (BCC) [unresectable locally advanced (laBCC) or metastatic (nodal or distant) (mBCC)] who had progressed on hedgehog pathway inhibitor (HHI) therapy, were intolerant of prior HHI therapy, or had no better than stable disease (SD) after 9 months on HHI therapy (exclusive of treatment breaks), were evaluated in Study 1620, an open-label, multi-centre, non-randomised study. The study excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 5 years; history of solid organ transplant; prior treatment with anti-PD-1/PD-L1 therapy or other immune checkpoint inhibitor therapy; infection with HIV, hepatitis B or hepatitis C; or ECOG performance score (PS) ≥ 2.
Patients received cemiplimab 350 mg intravenously (IV) every 3 weeks for 5 cycles of 9 weeks followed by 4 cycles of 12 weeks up to 93 weeks of treatment. Treatment continued until disease progression, unacceptable toxicity or completion of planned treatment. Tumour assessments were performed every 9 weeks during cycles 1 to 5 and every 12 weeks during cycles 6 to 9. The major efficacy endpoints were confirmed objective response rate (ORR) and duration of response (DOR) as assessed by independent central review (ICR). Secondary efficacy endpoints included ORR and DOR by investigator assessment (IA), progression free survival (PFS), overall survival (OS), complete response (CR) by ICR, time to tumour response (TTR), disease control rate (DCR), durable DCR by ICR, EORTC QLQ-C30 and Skindex-16 scores. For patients with mBCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1). For patients with externally visible target lesions (laBCC and mBCC), ORR was determined by a composite endpoint that integrated ICR assessments of radiologic data (RECIST 1.1) and digital medical photography (WHO criteria).
A total of 138 patients with advanced BCC were included in the efficacy analysis of study 1620. Of these, 39% had mBCC and 61% had laBCC. See Table 10 for a summary of baseline patient and disease characteristics.

The median time to response was 4.0 months (range 2.0 to 10.5 months) for the mBCC group, 4.3 months (range: 2.1 to 21 months) for the laBCC and 4.2 months overall (range: 2.0 to 21.4 months).
Forty patients (29.0%) with advanced BCC had complete response (CR) or partial response (PR).
ORR and PFS endpoints evaluated by investigator assessment (IA) were consistent with the independent central review results (ICR). Response rates were similar regardless of the reason for discontinuation of prior HHI therapy.
Efficacy results are presented in Table 11.

Efficacy and PD-L1 status.

Clinical activity was observed regardless of tumour PD-L1 expression status.
Elderly population. No overall differences in safety or effectiveness were observed between elderly patients and younger patients.

Libtayo as monotherapy.

Of the 1281 patients treated with cemiplimab monotherapy in clinical studies, 52.2% (669/1281) were less than 65 years, 25.9% (332/1281) were 65 to less than 75 years, and 21.9% (280/1281) were 75 years or older. Grade ≥ 3 adverse events occurred in 42.2% (140/ 332) of patients 65 to less than 75 years and 50.7% (142/280) of patients 75 years or older.
In the 193 advanced CSCC patients from study 1540 groups 1 to 3 in the efficacy analysis, the ORR by ICR (95% CI) was 42.9% (28.8%, 57.8%) in 49 of 193 patients less than 65 years, 53.0% (40.3%, 65.4%) in 66 of 193 patients 65 to less than 75 years, and 44.9% (33.6%, 56.6%) in 78 of 193 patients 75 years or older.
In the 710 advanced NSCLC patients in the efficacy analysis, the median OS (95% CI) was 24.4 months (17.3, NE) in the cemiplimab group and 17.1 months (12.1, 23.3) in the chemotherapy group in patients less than 65 years, was not reached (13.4, NE) in the cemiplimab group and 14.3 months (10.6, 22.3) in the chemotherapy group in patients 65 to less than 75 years, and 19.2 months (17.7, NE) in the cemiplimab group and 8.5 months (5.4, 14.2) in the chemotherapy group in patients 75 years or older. The median PFS by ICR (95% CI) was 6.2 months (4.3, 8.5) in the cemiplimab group and 5.6 months (4.2, 6.1) in the chemotherapy group in patients less than 65 years, 6.2 months (4.2, 8.2) in the cemiplimab group and 6.2 months (4.4, 6.2) in the chemotherapy group in patients 65 to less than 75 years, and 8.4 months (4.3, 19.1) in the cemiplimab group and 4.9 months (3.4, 6.2) in the chemotherapy group in patients 75 years or older.
In the 138 advanced BCC patients in the efficacy analysis, the objective response rate (ORR) by Independent Central Review (ICR) (95% CI) was 29.3% (18.1, 42.7) in 58 of 138 patients less than 65 years, 27.0% (13.8, 44.1) in 37 of 138 patients 65 to less than 75 years, and 30.2% (17.2, 46.1) in 43 of 138 patients 75 years or older.

Libtayo in combination with platinum‐based chemotherapy.

Among 466 advanced NSCLC patients in the efficacy analysis, 312 were treated with Libtayo and chemotherapy and 154 were treated with chemotherapy. Of the 312 patients receiving Libtayo and chemotherapy, 59% (184/312) were less than 65 years, 35.3% (110/312) were 65 to less than 75 years, and 5.8% (18/312) were 75 years or older. Grade ≥ 3 adverse events occurred in 40% (44/110) of patients 65 to less than 75 years and 55.6% (10/18) of patients 75 years or older.
The median OS (95% CI) was 21.9 months (15.6, NE) in the Libtayo and chemotherapy group and 12.6 months (9.3, 14.9) in the chemotherapy group in patients less than 65 years, 15.5 months (13.7, NE) in the Libtayo and chemotherapy group and 18 months (10.3, NE) in the chemotherapy group in patients 65 to less than 75 years, and was not reached (6, NE) in the Libtayo and chemotherapy group and 10.3 months (3.6, NE) in the chemotherapy group in patients 75 years or older.

5.2 Pharmacokinetic Properties

Concentration data from 1063 patients with various solid tumours who received cemiplimab were combined in a population PK analysis.
At 350 mg Q3W, the mean cemiplimab concentrations at steady-state ranged between a C_trough of 59 mg/L and a concentration at end of infusion (C_max) of 171 mg/L. Steady state exposure is achieved after approximately 4 months of treatment.
Cemiplimab exposure at steady-state in patients with solid tumours is similar at 350 mg Q3W and at 3 mg/kg Q2W.

Absorption.

Cemiplimab is administered via the intravenous route and hence is completely bioavailable.

Distribution.

Cemiplimab is primarily distributed in the vascular system with a volume of distribution at steady state (VSS) of 5.9 litres.

Metabolism.

Specific metabolism studies were not conducted because cemiplimab is a protein. Cemiplimab is expected to degrade to small peptides and individual amino acids.

Excretion.

Clearance of cemiplimab is linear at doses of 1 mg/kg to 10 mg/kg Q2W. Cemiplimab clearance after the first dose is approximately 0.25 L/day. The total clearance appears to decrease by approximately 11% over time, resulting in a steady state clearance (CL_ss) of 0.22 L/day; the decrease in CL is not considered clinically relevant. The within dosing interval half-life at steady state is 22 days.

Linearity/non-linearity.

At the dosing regimens of 1 mg/kg to 10 mg/kg every two weeks, pharmacokinetics of cemiplimab were linear and dose proportional, suggesting saturation of the systemic target-mediated pathway.