Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

LIBTAYO (BLA-761097)

(CEMIPLIMAB-RWLC)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

04/05/2024 (SUPPL-23)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions to Table 2 underlined:

Upper respiratory tract infectiong

g.         Upper respiratory tract infection is a composite term that includes upper respiratory tract infection, nasopharyngitis, sinusitis, influenza-like illness, rhinitis, influenza, viral upper respiratory tract infection, respiratory tract infection, influenza A virus test positive, and pharyngitis.

03/06/2024 (SUPPL-25)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

Additions and revisions underlined:

Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

04/28/2023 (SUPPL-15)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

Extensive changes; please refer to label for complete information

5.2 Infusion-Related Reactions

Additions and/or revisions underlined:

Severe or life-threatening infusion-related reactions occurred in 0.2% of patients receiving LIBTAYO as a single agent. Monitor patients for signs and symptoms of infusion-related reactions. Common symptoms of infusion-related reaction include nausea, pyrexia, and vomiting.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

LIBTAYO as a Single Agent

Of the 1281 patients who received LIBTAYO as a single agent in clinical studies, 26% were 65 years up to 75 years and 22% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 358 patients with mCSCC or laCSCC who received LIBTAYO as a single agent in Study 1540, 30% were 65 years up to 75 years and 48% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 138 patients with BCC who received LIBTAYO as a single agent in Study 1620, 27% were 65 years up to 75 years, and 31% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of

infusion reactions may include:

• nausea

• vomiting

…

What are the possible side effects of LIBTAYO?

…

The most common side effects of LIBTAYO when used alone include:

…

• low levels of red blood cells (anemia)

04/28/2023 (SUPPL-16)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

Extensive changes; please refer to label for complete information

5.2 Infusion-Related Reactions

Additions and/or revisions underlined:

Severe or life-threatening infusion-related reactions occurred in 0.2% of patients receiving LIBTAYO as a single agent. Monitor patients for signs and symptoms of infusion-related reactions. Common symptoms of infusion-related reaction include nausea, pyrexia, and vomiting.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

LIBTAYO as a Single Agent

Of the 1281 patients who received LIBTAYO as a single agent in clinical studies, 26% were 65 years up to 75 years and 22% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 358 patients with mCSCC or laCSCC who received LIBTAYO as a single agent in Study 1540, 30% were 65 years up to 75 years and 48% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 138 patients with BCC who received LIBTAYO as a single agent in Study 1620, 27% were 65 years up to 75 years, and 31% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of

infusion reactions may include:

• nausea

• vomiting

…

What are the possible side effects of LIBTAYO?

…

The most common side effects of LIBTAYO when used alone include:

…

• low levels of red blood cells (anemia)

11/08/2022 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

Newly added information:

The incidence and severity of immune-mediated adverse reactions were similar when LIBTAYO was administered as a single agent or in combination with chemotherapy.

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes related to new indication in certain patients with non-small cell lung cancer; please refer to label

8 Use in Specific Populations

8.1 Geriatric Use

Additions and revisions underlined:

LIBTAYO as a Single Agent

Of the 810 patients who received LIBTAYO as a single agent in clinical studies, 32% were 65 years up to 75 years and 22% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 219 patients with mCSCC or laCSCC who received LIBTAYO as a single agent in clinical studies, 34% were 65 years up to 75 years and 41% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 132 patients with BCC who received LIBTAYO as a single agent in Study 1620, 27% were 65 years up to 75 years, and 32% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

LIBTAYO in combination with Platinum-based Chemotherapy

Of the 312 patients with NSCLC who received LIBTAYO in combination with platinum-based chemotherapy in Study 16113, 35% were 65 years up to 75 years and 6% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Medication Guide

Additions and revisions underlined:

What is LIBTAYO?

LIBTAYO is a prescription medicine used to treat:

. . .

adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

o LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first

treatment when your lung cancer:

-has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or

chemotherapy with radiation, or

-your lung cancer has spread to other areas of your body (metastatic lung cancer), and

-your tumor does not have an abnormal “EGFR”, “ALK” or “ROS1” gene

o LIBTAYO may be used alone as your first treatment when your lung cancer:

-has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or

chemotherapy with radiation, or

-your lung cancer has spread to other areas of your body (metastatic lung cancer), and

-your tumor tests positive for high “PD-L1” and

-your tumor does not have an abnormal “EGFR”, “ALK” or “ROS1” gene

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 received an organ transplant

• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)

• have received radiation treatment to your chest area

• have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome

• are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby.

. . .

The most common side effects of LIBTAYO when used alone include:

• muscle or bone pain

• tiredness

• rash

• diarrhea

The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include:

• hair loss • tiredness

• muscle or bone pain • numbness, pain, tingling or burning in your hands or feet

• nausea • decreased appetite

Additions and/or revisions underlined:

What is Libatyo?

LIBTAYO is a prescription medicine used to treat:

people with …

• adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

  • LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer:

    • has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or

    • your lung cancer has spread to other areas of your body (metastatic lung cancer), and

    • your tumor does not have an abnormal “EGFR”, “ALK” or “ROS1” gene

  • LIBTAYO may be used alone as your first treatment when your lung cancer:

    • has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or

    • your lung cancer has spread to other areas of your body (metastatic lung cancer), and

    • your tumor tests positive for high “PD-L1” and

    • your tumor does not have an abnormal “EGFR”, “ALK” or “ROS1” gene

      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 received radiation treatment to your chest area

  …

  What are the possible side effects of LIBTAYO?

  …

  The most common side effects of LIBTAYO when used alone include:

• muscle or bone pain

• rash

• tiredness

• diarrhea

   

  The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include:

  • hair loss

  • tiredness

  • muscle or bone pain

  • numbness, pain, tingling or burning in your hands or feet

  • nausea

  • decreased appetite

02/22/2021 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

(Extensive changes; please refer to label)

5.2 Infusion-Related Reactions

(Additions and/or revisions underlined)

Severe infusion-related reactions (Grade 3) occurred in 0.1% of patients receiving LIBTAYO as a single agent. Monitor patients for signs and symptoms of infusion-related reactions. The most common symptoms of infusion-related reaction were nausea, pyrexia, rash and dyspnea.

Interrupt or slow the rate of infusion or permanently discontinue LIBTAYO based on severity of reaction [see Dosage and Administration (2.3)].

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive changes; please refer to label)

8 Use in Specific Populations

8.5 Geriatric Use

(Additions and/or revisions underlined)

Of the 810 patients who received LIBTAYO in clinical studies, 32% were 65 years up to 75 years and 22% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 219 patients with mCSCC or laCSCC who received LIBTAYO in clinical studies, 34% were 65 years up to 75 years and 41% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 132 patients with BCC who received LIBTAYO in Study 1620, 27% were 65 years up to 75 years, and 32% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Additions and/or revisions underlined)

…

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms which may include:

• chest pain, irregular heartbeat, shortness of breath or swelling of ankles

  confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs

• double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight

• persistent or severe muscle pain or weakness, muscle cramps

• low red blood cells, bruising

Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include:

• nausea                                          dizziness

• chills or shaking                            feel like passing out

• itching or rash                               fever

• flushing                                         back or neck pain

• shortness of breath or wheezing  facial swelling

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

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications.

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 also need to 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). LIBTAYO may be used to treat CSCC that has spread or cannot be cured by surgery or radiation.

• a type of skin cancer called basal cell carcinoma (BCC). LIBTAYO may be used when your BCC:

  • cannot be removed by surgery (locally advanced BCC) and you have received treatment with a hedgehog pathway inhibitor (HHI), or if you cannot receive treatment with a HHI.

  • has spread (metastatic BCC) and you have received treatment with a HHI, or if you cannot receive treatment with a HHI.

• a type of lung cancer called non-small cell lung cancer (NSCLC).

• LIBTAYO may be used as your first treatment when your lung cancer:

• has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or

• your lung cancer has spread to other areas of your body (metastatic lung cancer), and

• your tumor tests positive for high “PD-L1” and

• your tumor does not have an abnormal “EGFR”,” ALK “or “ROS1” gene

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

…

02/09/2021 (SUPPL-8)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive revisions; please refer to label)

6.2 Immunogenicity

(Additions and/or revisions underlined)

Anti-drug antibodies (ADA) were tested in 823 patients who received LIBTAYO. The incidence of cemiplimab-rwlc treatment-emergent ADAs was 2.2% using an electrochemiluminescent (ECL) bridging immunoassay; 0.4% 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

8.5 Geriatric Use

(Additions and/or revisions underlined)

Of the 219 patients with mCSCC or laCSCC who received LIBTAYO in clinical studies, 34% were 65 years up to 75 years and 41% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Of the 132 patients with BCC who received LIBTAYO in Study 1620, 27% were 65 years up to 75 years, and 32% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

11/10/2020 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

(Extensive changes; please refer to label)

5.3 Complications of Allogeneic HSCT

(Newly added subsection)

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

6 Adverse Reactions

(Additions and/or revisions underlined)

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)]

• Complications of Allogeneic HSCT [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

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 591 patients in two open-label, single-arm, multicohort studies (Study 1423 and Study 1540), including 131 patients with mCSCC (nodal or distant), 88 patients with locally advanced CSCC, and 372 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=470), 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=56). Among the 591 patients, 47% were exposed for greater than or equal to 6 months and 27% were exposed for greater than or equal to 12 months.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Extensive changes; please refer to label)

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Immune-Mediated Adverse Reactions

Advise patients that LIBTAYO 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.

Infusion-Related Reactions

Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2)].

Complications of Allogeneic HSCT or Solid Organ Transplant Rejection

Advise patients to contact their healthcare provider immediately if they develop signs or symptoms of post-allogeneic HSCT complications or of solid organ transplant rejection [see Warnings and Precautions (5.1, 5.3)].

Embryo-Fetal Toxicity

Advise females of reproductive potential that LIBTAYO can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1, 8.3)].

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)].

Lactation

Advise female patients not to breastfeed while taking LIBTAYO and for at least 4 months after the last dose [see Use in Specific Populations (8.2)].

06/25/2020 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

(Additions and/or revisions underlined)

LIBTAYO is a monoclonal antibody that belongs to a class of drugs that binds to the programmed death receptor-1 (PD-1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response with the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Warnings and Precautions may not be inclusive of all possible immune-mediated reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of

PD-1/PD-L1 blocking antibodies. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously.

…

Immune-Mediated Dermatologic Adverse Reactions

Immune-mediated dermatologic reactions, including erythema multiforme and pemphigoid, occurred in 1.7% of 534 patients receiving LIBTAYO, including Grade 3 (1.1%) and Grade 2 (0.6%) [see Adverse Reactions (6.1)]. In addition, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been observed with LIBTAYO and with other products in this class. Systemic corticosteroids were required in all patients with dermatologic reactions, including 89% who received prednisone ? 40 mg per day or equivalent. Dermatologic reactions resolved in 33% of patients. Approximately 22% of patients had recurrence of dermatologic reactions after re-initiation of LIBTAYO.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive changes; please refer to label)

6.2 Immunogenicity

(Additions and/or revisions underlined)

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 467 patients who received LIBTAYO. The incidence of cemiplimab-rwlc treatment-emergent ADAs was 1.1% using an electrochemiluminescent (ECL) bridging immunoassay; 0.2% 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

8.5 Geriatric Use

(Additions and/or revisions underlined)

Of the 219 mCSCC or laCSCC patients who received LIBTAYO in clinical studies, 34% were 65 years up to 75 years and 41% were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Extensive changes; please refer to label)