SPL MEDGUIDE SECTION.

This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: February 2021MEDICATION GUIDE LIBTAYO(R) (Lib-TIE-oh) (cemiplimab-rwlc) injectionWhat is the most important information should know about LIBTAYOLIBTAYO is medicine that may treat certain types of cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems.coughshortness of breathchest painIntestinal problems.diarrhea (loose stools) or more frequent bowel movements than usualstools that are black, tarry, sticky, or have blood or mucussevere stomach-area (abdomen) pain or tendernessLiver problems.yellowing of your skin or the whites of your eyessevere nausea or vomitingpain on the right side of your stomach-area (abdomen)dark urine (tea colored)bleeding or bruising more easily than normalHormone gland problems.headache that will not go away or unusual headacheseye sensitivity to light eye problemsrapid heartbeatincreased sweatingextreme tirednessweight gain or weight lossfeeling more hungry or thirsty than usualurinating more often than usual hair lossfeeling coldconstipationyour voice gets deeperdizziness or faintingchanges in mood or behavior, such as decreased sex drive, irritability, or forgetfulnessKidney problems.decrease in your amount of urineblood in your urineswelling of your anklesloss of appetiteSkin problems.rashitchingskin blistering or peelingpainful sores or ulcers in mouth or nose, throat, or genital areafever or flu-like symptomsswollen lymph nodesProblems 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 anklesconfusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legsdouble vision, blurry vision, sensitivity to light, eye pain, changes in eyesightpersistent or severe muscle pain or weakness, muscle crampslow red blood cells, bruisingInfusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include:nauseachills or shakingitching or rashflushingshortness of breath or wheezingdizzinessfeel like passing outfeverback or neck painfacial swellingRejection of 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 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 LIBTAYOLIBTAYO is prescription medicine used to treat people with: 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 hedgehog pathway inhibitor (HHI), or if you cannot receive treatment with HHI.has spread (metastatic BCC) and you have received treatment with HHI, or if you cannot receive treatment with HHI. 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. Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you:have immune system problems such as Crohns disease, ulcerative colitis, or lupushave received an organ transplanthave received or plan to receive stem cell transplant that uses donor stem cells (allogeneic)have condition that affects your nervous system, such as myasthenia gravis or Guillain-Barre syndromeare pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider will give you pregnancy test before you start treatment with LIBTAYO. You should use an effective method of birth control during your treatment and for at least months after the last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO. are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least months after the last dose of LIBTAYO.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive LIBTAYOYour healthcare provider will give you LIBTAYO into your vein through an intravenous (IV) line over 30 minutes.LIBTAYO is usually given every weeks.Your healthcare provider will decide how many treatments you will need.Your healthcare provider will do blood tests to check you for side effects.If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.What are the possible side effects of LIBTAYOLIBTAYO can cause serious side effects, including:See What is the most important information should know about LIBTAYOThe most common side effects of LIBTAYO include muscle or bone pain, tiredness, rash, and diarrhea.These are not all the possible side effects of LIBTAYO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of LIBTAYO.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. If you would like more information about LIBTAYO, talk with your healthcare provider. You can ask your healthcare provider for information about LIBTAYO that is written for health professionals.What are the ingredients of LIBTAYOActive ingredient: cemiplimab-rwlc Inactive ingredients: L-histidine, L-histidine monohydrochloride monohydrate, sucrose, L-proline, Polysorbate 80, and Water for Injection, USP.Manufactured by: Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591-6707 U.S. License No. 1760 Marketed by: Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591) and sanofi-aventis U.S. LLC (Bridgewater, NJ 08807) For more information, call 1-877-542-8296 (C)2021 Regeneron Pharmaceuticals, Inc/sanofi-aventis U.S. LLC. All rights reserved.. cough. shortness of breath. chest pain. diarrhea (loose stools) or more frequent bowel movements than usual. stools that are black, tarry, sticky, or have blood or mucus. severe stomach-area (abdomen) pain or tenderness. yellowing of your skin or the whites of your eyes. severe nausea or vomiting. pain on the right side of your stomach-area (abdomen). dark urine (tea colored). bleeding or bruising more easily than normal. headache that will not go away or unusual headaches. eye sensitivity to light eye problems. rapid heartbeat. increased sweating. extreme tiredness. weight gain or weight loss. feeling more hungry or thirsty than usual. urinating more often than usual hair loss. feeling cold. constipation. your voice gets deeper. dizziness or fainting. changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness. decrease in your amount of urine. blood in your urine. swelling of your ankles. loss of appetite. rash. itching. skin blistering or peeling. painful sores or ulcers in mouth or nose, throat, or genital area. fever or flu-like symptoms. swollen lymph nodes. 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. nausea. chills or shaking. itching or rash. flushing. shortness of breath or wheezing. dizziness. feel like passing out. fever. back or neck pain. facial swelling. 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.. 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 hedgehog pathway inhibitor (HHI), or if you cannot receive treatment with HHI.has spread (metastatic BCC) and you have received treatment with HHI, or if you cannot receive treatment with HHI. cannot be removed by surgery (locally advanced BCC) and you have received treatment with hedgehog pathway inhibitor (HHI), or if you cannot receive treatment with HHI.. has spread (metastatic BCC) and you have received treatment with HHI, or if you cannot receive treatment with HHI.. 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 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 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. have immune system problems such as Crohns disease, ulcerative colitis, or lupus. have received an organ transplant. have received or plan to receive stem cell transplant that uses donor stem cells (allogeneic). have condition that affects your nervous system, such as myasthenia gravis or Guillain-Barre syndrome. are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider will give you pregnancy test before you start treatment with LIBTAYO. You should use an effective method of birth control during your treatment and for at least months after the last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO. Your healthcare provider will give you pregnancy test before you start treatment with LIBTAYO. You should use an effective method of birth control during your treatment and for at least months after the last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO.. are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least months after the last dose of LIBTAYO.. Your healthcare provider will give you LIBTAYO into your vein through an intravenous (IV) line over 30 minutes.. LIBTAYO is usually given every weeks.. Your healthcare provider will decide how many treatments you will need.. Your healthcare provider will do blood tests to check you for side effects.. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.. See What is the most important information should know about LIBTAYO.

ADVERSE REACTIONS SECTION.

6ADVERSE REACTIONS. The following serious adverse reactions are described elsewhere in the labeling.Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] Infusion-Related Reactions [see Warnings and Precautions (5.2)] Complications of Allogeneic HSCT [see Warnings and Precautions (5.3)] 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)] The most common adverse reactions (>=15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 laboratory abnormalities (>=2%) were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-877-542-8296 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 as single agent in 810 patients in three open-label, single-arm, multicohort studies (Study 1423, Study 1540 and Study 1620), and one open-label randomized multi-center study (Study 1624). These studies included 219 patients with advanced CSCC (Studies 1540 and 1423), 132 patients with advanced BCC (Study 1620), 355 patients with NSCLC (Study 1624), and 104 patients with other advanced solid tumors (Study 1423). LIBTAYO was administered intravenously at doses of mg/kg every weeks (n=235), 350 mg every weeks (n=543), or other doses (n=32; mg/kg every weeks, 10 mg/kg every weeks, 200 mg every weeks). Among the 810 patients, 57% were exposed for >= months and 25% were exposed for >= 12 months. In this pooled safety population, the most common adverse reactions (>=15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 laboratory abnormalities (>=2%) were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia.. Cutaneous Squamous Cell Carcinoma (CSCC)The safety of LIBTAYO was evaluated in 219 patients with advanced CSCC (metastatic or locally advanced disease) in Study 1423 and Study 1540 [see Clinical Studies (14.1)]. Of these 219 patients, 131 had mCSCC (nodal or distant) and 88 had laCSCC. Patients received LIBTAYO mg/kg every weeks (n=1), mg/kg every weeks (n=162) or 350 mg every weeks (n=56) as an intravenous infusion until disease progression, unacceptable toxicity, or completion of planned treatment. The median duration of exposure was 38 weeks (2 weeks to 110 weeks).The safety population characteristics were: median age of 72 years (38 to 96 years), 83% male, 96% White, and European Cooperative Oncology Group (ECOG) performance score (PS) of (44%) and (56%).Serious adverse reactions occurred in 35% of patients. Serious adverse reactions that occurred in at least 2% of patients were pneumonitis, cellulitis, sepsis, and pneumonia.Permanent discontinuation due to an adverse reaction occurred in 8% of patients. Adverse reactions resulting in permanent discontinuation were pneumonitis, cough, pneumonia, encephalitis, aseptic meningitis, hepatitis, arthralgia, muscular weakness, neck pain, soft tissue necrosis, complex regional pain syndrome, lethargy, psoriasis, rash maculopapular, proctitis, and confusional state.The most common (>= 20%) adverse reactions were fatigue, rash, diarrhea, musculoskeletal pain, and nausea. The most common Grade or adverse reactions (>= 2%) were cellulitis, anemia, hypertension, pneumonia, musculoskeletal pain, fatigue, pneumonitis, sepsis, skin infection, and hypercalcemia. The most common (>= 4%) Grade or laboratory abnormalities worsening from baseline were lymphopenia, anemia, hyponatremia, and hypophosphatemia.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities worsening from baseline in >= 1% of patients receiving LIBTAYO.Table 2:Adverse Reactions in >= 10% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540Adverse ReactionsLIBTAYO = 219All Grades %Grades 3-4 %Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03General and Administration Site FatigueComposite term includes fatigue and asthenia 343Skin and Subcutaneous Tissue RashComposite term includes rash, rash maculopapular, erythema, dermatitis, dermatitis bullous, rash generalized, pemphigoid, rash erythematous, rash macular, rash pruritic, drug eruption, psoriasis, and skin reaction 311 PruritusComposite term includes pruritus and pruritus allergic 180Gastrointestinal DiarrheaComposite term includes diarrhea and colitis 250.5 Nausea210 Constipation130.5 Vomiting100.5Musculoskeletal and Connective Tissue Musculoskeletal painComposite term includes back pain, pain in extremity, myalgia, musculoskeletal pain, and neck pain 243 Arthralgia111Respiratory CoughComposite term includes cough and upper airway cough syndrome 140Hematology Anemia114Endocrine Hypothyroidism100Metabolism and Nutrition Decreased appetite100Table 3:Grade or Laboratory Abnormalities Worsening from Baseline in >= 1% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540Laboratory AbnormalityGrade 3-4 (%)Percentages are based on the number of patients with at least post-baseline value available for that parameter Toxicity graded per NCI CTCAE v. 4.03Chemistry Increased aspartate aminotransferase2 Increased INR2Hematology Lymphopenia9 Anemia5Electrolytes Hyponatremia5 Hypophosphatemia4 Hypercalcemia2. Basal Cell Carcinoma (BCC)The safety of LIBTAYO was evaluated in 132 patients with advanced BCC (mBCC N=48, laBCC N=84) in an open-label, single-arm trial (Study 1620) [see Clinical Studies (14.2)]. Patients received LIBTAYO 350 mg every weeks as an intravenous infusion for up to 93 weeks or until disease progression or unacceptable toxicity. The median duration of exposure was 42 weeks (range: 2.1 weeks to 94 weeks).The safety population characteristics were: median age of 68 years (38 to 90 years), 67% male, 74% White, and ECOG performance score (PS) of (62%) and (38%).Serious adverse reactions occurred in 32% of patients. Serious adverse reactions that occurred in 1.5% (at least patients) were urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm, and somnolence. Fatal adverse reactions occurred in 1.5% of patients who received LIBTAYO, including acute kidney injury and cachexia.Permanent discontinuation of LIBTAYO due to an adverse reaction occurred in 13% of patients. Adverse reactions resulting in permanent discontinuation of LIBTAYO in 1.5% (at least patients) were colitis and general physical health deterioration.Dosage delays of LIBTAYO due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage delay in 2% of patients (at least patients) included blood creatinine increased, diarrhea, colitis, fatigue, headache, pneumonitis, and urinary tract infection.The most common adverse reactions reported in at least 15% of patients were fatigue, musculoskeletal pain, diarrhea, rash, pruritus, and upper respiratory tract infection.The most common Grade or adverse reactions (> 2%) were hypertension, colitis, fatigue, urinary tract infection, pneumonia, increased blood pressure, hypokalemia and visual impairment. The most common (> 3%) laboratory abnormality worsening from baseline to Grade or was hyponatremia.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities worsening from baseline in >= 1% of patients receiving LIBTAYO.Table 4:Adverse Reactions in >= 10% of Patients with Advanced BCC Receiving LIBTAYO in Study 1620Adverse ReactionsLIBTAYO = 132All Grades %Grades 3-4 %Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03General disorders and administration site conditions FatigueComposite term includes fatigue, asthenia, and malaise 493.8Musculoskeletal and connective tissue disorders Musculoskeletal painComposite term includes arthralgia, back pain, myalgia, pain in extremity, musculoskeletal pain, neck pain, musculoskeletal stiffness, musculoskeletal chest pain, musculoskeletal discomfort, and spinal pain 331.5Gastrointestinal disorders Diarrhea250 Nausea120.8 Constipation110.8Skin and subcutaneous tissue disorders RashComposite term includes rash maculo-papular, rash, dermatitis, dermatitis acneiform, erythema, rash pruritic, dermatitis bullous, dyshidrotic eczema, pemphigoid, rash erythematous, and urticaria 220.8 Pruritus200Infections and infestations Upper respiratory tract infectionComposite term includes upper respiratory tract infection, nasopharyngitis, rhinitis, sinusitis, pharyngitis, respiratory tract infection, and viral upper respiratory tract infection 150 Urinary tract infection122.3Metabolism and nutrition disorders Decreased appetite141.5Blood and lymphatic system disorders Anemia130.8Nervous system disorders Headache121.5Respiratory, thoracic and mediastinal disorders DyspneaComposite term includes dyspnea and dyspnea exertional 110Vascular disorders HypertensionComposite term includes hypertension and hypertensive crisis 114.5Table 5:Grade or Laboratory Abnormalities Worsening from Baseline in >= 1% of Patients with Advanced BCC Receiving LIBTAYO in Study 1620Laboratory AbnormalityGrade 3-4 (%)Percentages are based on the number of patients with at least post-baseline value available for that parameter Toxicity graded per NCI CTCAE v. 4.03Electrolytes Hyponatremia3.1 Hypokalemia1.5Coagulation Activated partial thromboplastin time prolonged2.3Hematology Lymphocyte count decreased2.3. Non-Small Cell Lung Cancer (NSCLC)The safety of LIBTAYO was evaluated in 355 patients with locally advanced or metastatic NSCLC in Study 1624 [see Clinical Studies (14.3)]. Patients received LIBTAYO 350 mg every weeks (n=355) or investigators choice of chemotherapy (n=342), consisting of paclitaxel plus cisplatin or carboplatin; gemcitabine plus cisplatin or carboplatin; or pemetrexed plus cisplatin or carboplatin followed by optional pemetrexed maintenance. The median duration of exposure was 27.3 weeks (9 days to 115 weeks) in the LIBTAYO group and 17.7 weeks (18 days to 86.7 weeks) in the chemotherapy group. In the LIBTAYO group, 54% of patients were exposed to LIBTAYO for >= months and 22 were exposed for >= 12 months.The safety population characteristics were: median age of 63 years (31 to 79 years), 44% of patients 65 or older, 88% male, 86%White, 82% had metastatic disease and 18% had locally advanced disease and ECOG performance score (PS) of (27%) and (73%).LIBTAYO was permanently discontinued due to adverse reactions in 6% of patients; adverse reactions resulting in permanent discontinuation in at least patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. Serious adverse reactions occurred in 28% of patients. The most frequent serious adverse reactions in at least 2% of patients were pneumonia and pneumonitis.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities in patients receiving LIBTAYO.Table 6: Adverse Reactions in >= 10% of Patients with Locally Advanced or Metastatic NSCLC Receiving LIBTAYO in Study 1624Adverse ReactionsLIBTAYON=355ChemotherapyN=342All Grades%Grades 3-4%All Grades%Grades 3-4%Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03Musculoskeletal and connective tissue disorders Musculoskeletal painMusculoskeletal pain is composite term that includes back pain, arthralgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, bone pain, myalgia, neck pain, spinal pain, and musculoskeletal stiffness 260.6271.5Skin and subcutaneous tissue disorders RashRash is composite term that includes rash, dermatitis, urticaria, rash maculo-papular, erythema, rash erythematous, rash pruritic, psoriasis, autoimmune dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, drug eruption, dyshidrotic eczema, lichen planus, and skin reaction 151.460Blood and lymphatic system disorders Anemia153.45016General disorders and administration site conditions FatigueFatigue is composite term that includes fatigue, asthenia, and malaise 141.1262Metabolism and nutrition disorders Decreased appetite120.6180.3Infections and infestations PneumoniaPneumonia is composite term that includes atypical pneumonia, embolic pneumonia, lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia bacterial, and pneumonia klebsiella 115125Respiratory, thoracic and mediastinal disorders CoughCough is composite term that includes cough and productive cough 11080.3Table 7: Grade or Laboratory Abnormalities Worsening from Baseline in >=1% of Patients with Locally Advanced or Metastatic NSCLC Receiving LIBTAYO in Study 1624Laboratory AbnormalityLIBTAYON=355ChemotherapyN=342Grades 3-4Percentages are based on the number of patients with at least post-baseline value available for that parameter. %Toxicity graded per NCI CTCAE v. 4.03Chemistry Increased aspartate aminotransferase3.91.2 Increased alanine aminotransferase2.70.3 Increased alkaline phosphatase2.40.3 Increased blood bilirubin2.10.3 Hypoalbuminemia1.81.3 Increased creatinine1.21.6Hematology Lymphopenia79 Anemia2.716Electrolytes Hyponatremia67 Hyperkalemia4.21.9 Hypocalcemia3.93.4 Hypophosphatemia2.44.1 Hypermagnesemia2.11.6 Hypokalemia1.52.2 Hypercalcemia1.22.2. 6.2Immunogenicity. As with all therapeutic proteins, there is 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 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.

CLINICAL STUDIES SECTION.

14CLINICAL STUDIES. 14.1 Cutaneous Squamous Cell Carcinoma (CSCC). The efficacy of LIBTAYO in 219 patients with metastatic (nodal or distant) cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who were not candidates for curative surgery or curative radiation was evaluated in two open-label, multi-center, non-randomized, multicohort studies: Study 1423 (NCT02383212) and Study 1540 (NCT02760498). Both studies excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within years; history of solid organ transplant; prior treatment with anti-PD-1/PD-L1 blocking antibodies or other immune checkpoint inhibitor therapy; infection with HIV, hepatitis or hepatitis C; or ECOG PS >= 2.Patients received LIBTAYO mg/kg intravenously every weeks for up to 48 weeks in Study 1423 or up to 96 weeks in Study 1540. An additional cohort of patients in Study 1540 received 350 mg every weeks for up to 54 weeks. Treatment continued until progression of disease, unacceptable toxicity, or completion of planned treatment. Tumor response assessments were performed every or weeks. The major efficacy outcome measures were confirmed objective response rate (ORR), defined as complete response (CR) plus partial response (PR) as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR). For patients with mCSCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). For patients with externally visible target lesions (laCSCC and mCSCC), ORR was determined by composite endpoint that integrated ICR assessments of radiologic data (RECIST 1.1) and digital medical photography (WHO criteria).. Study 1540Among the 193 patients with advanced CSCC enrolled in Study 1540 who received LIBTAYO at either mg/kg every weeks or 350 mg every three weeks, 115 had mCSCC and 78 had laCSCC. The median age was 72 years (38 to 96 years); 83% were male; 97% were White; 45% had ECOG PS and 55% had ECOG PS 1; 34% received at least one prior anti-cancer systemic therapy; 90% received prior cancer-related surgery; and 68% received prior radiotherapy. Among patients with mCSCC, 77% had distant metastases and 23% had only nodal metastases.For the responding patients presented in Table below, the median time to response was 1.9 months (range: 1.7 to 9.1 months).Efficacy results in patients who received mg/kg every weeks are presented in Table 8.Table 8:Efficacy Results for Study 1540 in CSCC: mg/kg every weeksEfficacy EndpointsMedian duration of follow up: mCSCC: 16.5 months; laCSCC: 9.3 months; combined CSCC: 11.1 months Metastatic CSCC LIBTAYO mg/kg every weeksLocally Advanced CSCC LIBTAYO mg/kg every weeksCombined CSCCN 59N 78N 137CI: confidence interval; NR: Not reached; +: Denotes ongoing at last assessmentConfirmed Objective Response Rate (ORR)ORR49%44%46%(95% CI)(36, 63)(32, 55)(37, 55) Complete response17% 13%15% (95% CI)Only includes patients with complete healing of prior cutaneous involvement; laCSCC patients in Study 1540 required biopsy to confirm CR (8, 29)(6, 22)(9, 22) Partial response32%31%31% (95% CI)(21, 46)(21, 42)(24, 40)Duration of Response (DOR)Median DOR in months (Range)NR(2.8 21.6+)NR(1.9 24.2+)NR(1.9 24.2+)Patients with observed DOR >= months, (%)The numerator includes the number of patients whose observed DOR reached at least the specified times of or 12 months. Patients who did not have the opportunity to reach the specified timepoint were included in the denominator only 27 (93%)23 (68%)50 (79%)Patients with observed DOR >= 12 months, (%) 22 (76%)12 (35%)34 (54%). Study 1540: 350 mg every weeksIn an additional cohort in Study 1540, 56 patients received cemiplimab-rwlc at dose of 350 mg intravenously every weeks for up to 54 weeks. With median duration of follow-up of 8.0 months, the confirmed ORR was 41% (95% CI: 28, 55), and 65% of responders had DOR >= months.. Study 1423Among 26 CSCC patients in Study 1423, 16 had mCSCC and 10 had laCSCC. The median age was 73 years (52 to 88 years); 81% of patients were male; 92% of patients were White; the ECOG PS was (38%) and (62%); 58% of patients had received at least prior anti-cancer systemic therapy; 92% of patients had received prior cancer-related surgery and 81% had received prior radiotherapy. One patient in the mCSCC group was dosed at mg/kg. The rest received mg/kg every weeks.With median duration of follow-up of 13.3 months, the confirmed ORR was 50% (95% CI: 30, 70); all responses were PRs. The median time to response was 1.9 months (range: 1.7 to 7.3 months) and 85% of responders had DOR >= months.. 14.2 Basal Cell Carcinoma (BCC). The efficacy of LIBTAYO in 112 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, had not had an objective response after months on HHI therapy, or were intolerant of prior HHI therapy was evaluated in Study 1620 (NCT03132636), an open-label, multi-center, non-randomized study. The study excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 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 or hepatitis C; or ECOG performance score (PS) >= 2.Patients received LIBTAYO 350 mg every weeks for up to 93 weeks until disease progression, unacceptable toxicity, or completion of planned treatment. Tumor assessments were performed every weeks for the first 45 weeks of treatment and every 12 weeks thereafter. The major efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR) as assessed by independent central review (ICR). For patients with mBCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). For patients with externally visible target lesions (laBCC and mBCC), ORR was determined by composite endpoint that integrated ICR assessments of radiologic data (RECIST 1.1) and digital medical photography (WHO criteria).A total of 112 patients with advanced BCC were included in the efficacy analysis of Study 1620. Of these, 25% had mBCC and 75% had laBCC. In patients with laBCC, the median age was 70 years (42 to 89 years); 67% were male; 68% were White; 61% had ECOG PS and 39% had ECOG PS 1; 83% had received at least prior cancer-related surgery; and 50% had received prior radiotherapy. In patients with mBCC, the median age was 65.5 years (38 to 90 years); 82% were male; 79% were White; 57% had ECOG PS and 43% had ECOG PS 1; 82% had received at least prior cancer-related surgery; and 61% had received prior radiotherapy. Among patients with mBCC, 32% had distant metastases only, 14% had nodal disease only, and 54% had both distant and nodal disease.Efficacy results are presented in Table 9. For the responding patients, the median time to response was 3.2 months (range 2.1 to 10.5 months) for the mBCC group and 4.2 months (range 2.1 to 13.4 months) for the laBCC group.Table 9:Efficacy Results for Study 1620 in BCCEfficacy EndpointsMedian duration of follow up: mBCC 9.5 months; laBCC 15.1 months Metastatic BCCLocally Advanced BCCN 28N 84CI: confidence interval; NR: Not reached; +: Denotes ongoing at last assessmentConfirmed Objective Response Rate (ORR) ORR, (%)6 (21%)24 (29%) (95% CI)(8, 41)(19, 40) Complete response, (%)05 (6%) Partial response, (%)6 (21%)19 (23%)Duration of Response (DOR) Median DOR in monthsNRNR (Range)(9.0 23.0+)(2.1 21.4+) Patients with observed DOR >= months, (%)6 (100%)19 (79.2%). 14.3Non-Small Cell Lung Cancer (NSCLC). The efficacy of LIBTAYO was evaluated in Study 1624 (NCT03088540), randomized, multi-center, open-label, active-controlled trial in 710 patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation, or with metastatic NSCLC.Only patients whose tumors had high PD-L1 expression [Tumor Proportion Score (TPS) >= 50%] as determined by an immunohistochemistry assay using the PD-L1 IHC 22C3 pharmDx kit and who had not received prior systemic treatment for metastatic NSCLC were eligible.Patients with EGFR, ALK or ROS1 genomic tumor aberrations; medical condition that required systemic immunosuppression; autoimmune disease that required systemic therapy within years of treatment; or who had never smoked were ineligible. Patients with history of brain metastases were eligible if they had been adequately treated and had neurologically returned to baseline for at least weeks prior to randomization.Randomization was stratified by histology (non-squamous vs squamous) and geographic region (Europe vs Asia vs Rest of world). Patients were randomized (1:1) to receive LIBTAYO 350 mg intravenously (IV) every weeks for up to 108 weeks or platinum-doublet chemotherapy regimen for to cycles followed by optional pemetrexed maintenance for patients with non-squamous histology who received pemetrexed containing regimen.Treatment with LIBTAYO 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 LIBTAYO therapy were permitted to continue treatment with LIBTAYO (up to an additional 108 weeks) with the addition of cycles of histology-specific chemotherapy until further progression was observed. Of the 203 patients randomized to receive chemotherapy who had IRC-assessed RECIST 1.1- defined disease progression, 150 (74%) patients crossed over to treatment with LIBTAYO. Assessment of tumor status was performed every weeks. The major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS). An additional efficacy outcome measure was overall response rate (ORR).The study population characteristics were: median age of 63 years (range: 31 to 84 years), 45% age 65 or older; 85% male; 86% White, 11% Asian; and 0.6% Black. Nine percent were Hispanic or Latino. Twenty-seven percent had ECOG PS and 73% had ECOG PS 1; 84% had metastatic disease and 16% had stage IIIB or IIIC disease and were not candidates for surgical resection or definitive chemoradiation per investigator assessment; 56% had non-squamous and 44% had squamous histology; and 12% had history of treated brain metastases at baseline.The trial demonstrated statistically significant improvement in OS and PFS for patients randomized to LIBTAYO as compared with chemotherapy.Efficacy results are presented in Table 10 and Figure 1.Table 10: Efficacy Results from Study 1624 in Non-Small Cell Lung CancerEndpointsLIBTAYON=356ChemotherapyN=354BICR: blinded independent central review, CI: confidence interval; NE: Not evaluable; +: Ongoing responseOverall Survival Number of deaths (%)108 (30)141 (40) Median in months (95% CI)Based on Kaplan-Meier method 22.1 (17.7, NE)14.3 (11.7, 19.2) Hazard ratio (95% CI)Based on stratified proportional hazards model 0.68 (0.53, 0.87) p-value0.0022Progression-free Survival per BICR Number of events (%)201 (57)262 (74) Median in months (95% CI) 6.2 (4.5, 8.3)5.6 (4.5, 6.1) Hazard ratio (95% CI) 0.59 (0.49, 0.72) p-value<0.0001Overall Response Rate per BICR (%)Clopper-Pearson exact confidence interval ORR (95% CI)37 (32, 42)21 (17, 25) Complete response (CR) rate31 Partial response (PR) rate3320Duration of Response per BICR Median in months (range)21.0 (1.9+, 23.3+)6.0 (1.3+, 16.5+)Figure 1:Kaplan-Meier Curve for OS from Study 1624. Figure 1.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 as single agent in 810 patients in three open-label, single-arm, multicohort studies (Study 1423, Study 1540 and Study 1620), and one open-label randomized multi-center study (Study 1624). These studies included 219 patients with advanced CSCC (Studies 1540 and 1423), 132 patients with advanced BCC (Study 1620), 355 patients with NSCLC (Study 1624), and 104 patients with other advanced solid tumors (Study 1423). LIBTAYO was administered intravenously at doses of mg/kg every weeks (n=235), 350 mg every weeks (n=543), or other doses (n=32; mg/kg every weeks, 10 mg/kg every weeks, 200 mg every weeks). Among the 810 patients, 57% were exposed for >= months and 25% were exposed for >= 12 months. In this pooled safety population, the most common adverse reactions (>=15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 laboratory abnormalities (>=2%) were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia.. Cutaneous Squamous Cell Carcinoma (CSCC)The safety of LIBTAYO was evaluated in 219 patients with advanced CSCC (metastatic or locally advanced disease) in Study 1423 and Study 1540 [see Clinical Studies (14.1)]. Of these 219 patients, 131 had mCSCC (nodal or distant) and 88 had laCSCC. Patients received LIBTAYO mg/kg every weeks (n=1), mg/kg every weeks (n=162) or 350 mg every weeks (n=56) as an intravenous infusion until disease progression, unacceptable toxicity, or completion of planned treatment. The median duration of exposure was 38 weeks (2 weeks to 110 weeks).The safety population characteristics were: median age of 72 years (38 to 96 years), 83% male, 96% White, and European Cooperative Oncology Group (ECOG) performance score (PS) of (44%) and (56%).Serious adverse reactions occurred in 35% of patients. Serious adverse reactions that occurred in at least 2% of patients were pneumonitis, cellulitis, sepsis, and pneumonia.Permanent discontinuation due to an adverse reaction occurred in 8% of patients. Adverse reactions resulting in permanent discontinuation were pneumonitis, cough, pneumonia, encephalitis, aseptic meningitis, hepatitis, arthralgia, muscular weakness, neck pain, soft tissue necrosis, complex regional pain syndrome, lethargy, psoriasis, rash maculopapular, proctitis, and confusional state.The most common (>= 20%) adverse reactions were fatigue, rash, diarrhea, musculoskeletal pain, and nausea. The most common Grade or adverse reactions (>= 2%) were cellulitis, anemia, hypertension, pneumonia, musculoskeletal pain, fatigue, pneumonitis, sepsis, skin infection, and hypercalcemia. The most common (>= 4%) Grade or laboratory abnormalities worsening from baseline were lymphopenia, anemia, hyponatremia, and hypophosphatemia.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities worsening from baseline in >= 1% of patients receiving LIBTAYO.Table 2:Adverse Reactions in >= 10% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540Adverse ReactionsLIBTAYO = 219All Grades %Grades 3-4 %Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03General and Administration Site FatigueComposite term includes fatigue and asthenia 343Skin and Subcutaneous Tissue RashComposite term includes rash, rash maculopapular, erythema, dermatitis, dermatitis bullous, rash generalized, pemphigoid, rash erythematous, rash macular, rash pruritic, drug eruption, psoriasis, and skin reaction 311 PruritusComposite term includes pruritus and pruritus allergic 180Gastrointestinal DiarrheaComposite term includes diarrhea and colitis 250.5 Nausea210 Constipation130.5 Vomiting100.5Musculoskeletal and Connective Tissue Musculoskeletal painComposite term includes back pain, pain in extremity, myalgia, musculoskeletal pain, and neck pain 243 Arthralgia111Respiratory CoughComposite term includes cough and upper airway cough syndrome 140Hematology Anemia114Endocrine Hypothyroidism100Metabolism and Nutrition Decreased appetite100Table 3:Grade or Laboratory Abnormalities Worsening from Baseline in >= 1% of Patients with Advanced CSCC Receiving LIBTAYO in Study 1423 and Study 1540Laboratory AbnormalityGrade 3-4 (%)Percentages are based on the number of patients with at least post-baseline value available for that parameter Toxicity graded per NCI CTCAE v. 4.03Chemistry Increased aspartate aminotransferase2 Increased INR2Hematology Lymphopenia9 Anemia5Electrolytes Hyponatremia5 Hypophosphatemia4 Hypercalcemia2. Basal Cell Carcinoma (BCC)The safety of LIBTAYO was evaluated in 132 patients with advanced BCC (mBCC N=48, laBCC N=84) in an open-label, single-arm trial (Study 1620) [see Clinical Studies (14.2)]. Patients received LIBTAYO 350 mg every weeks as an intravenous infusion for up to 93 weeks or until disease progression or unacceptable toxicity. The median duration of exposure was 42 weeks (range: 2.1 weeks to 94 weeks).The safety population characteristics were: median age of 68 years (38 to 90 years), 67% male, 74% White, and ECOG performance score (PS) of (62%) and (38%).Serious adverse reactions occurred in 32% of patients. Serious adverse reactions that occurred in 1.5% (at least patients) were urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm, and somnolence. Fatal adverse reactions occurred in 1.5% of patients who received LIBTAYO, including acute kidney injury and cachexia.Permanent discontinuation of LIBTAYO due to an adverse reaction occurred in 13% of patients. Adverse reactions resulting in permanent discontinuation of LIBTAYO in 1.5% (at least patients) were colitis and general physical health deterioration.Dosage delays of LIBTAYO due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage delay in 2% of patients (at least patients) included blood creatinine increased, diarrhea, colitis, fatigue, headache, pneumonitis, and urinary tract infection.The most common adverse reactions reported in at least 15% of patients were fatigue, musculoskeletal pain, diarrhea, rash, pruritus, and upper respiratory tract infection.The most common Grade or adverse reactions (> 2%) were hypertension, colitis, fatigue, urinary tract infection, pneumonia, increased blood pressure, hypokalemia and visual impairment. The most common (> 3%) laboratory abnormality worsening from baseline to Grade or was hyponatremia.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities worsening from baseline in >= 1% of patients receiving LIBTAYO.Table 4:Adverse Reactions in >= 10% of Patients with Advanced BCC Receiving LIBTAYO in Study 1620Adverse ReactionsLIBTAYO = 132All Grades %Grades 3-4 %Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03General disorders and administration site conditions FatigueComposite term includes fatigue, asthenia, and malaise 493.8Musculoskeletal and connective tissue disorders Musculoskeletal painComposite term includes arthralgia, back pain, myalgia, pain in extremity, musculoskeletal pain, neck pain, musculoskeletal stiffness, musculoskeletal chest pain, musculoskeletal discomfort, and spinal pain 331.5Gastrointestinal disorders Diarrhea250 Nausea120.8 Constipation110.8Skin and subcutaneous tissue disorders RashComposite term includes rash maculo-papular, rash, dermatitis, dermatitis acneiform, erythema, rash pruritic, dermatitis bullous, dyshidrotic eczema, pemphigoid, rash erythematous, and urticaria 220.8 Pruritus200Infections and infestations Upper respiratory tract infectionComposite term includes upper respiratory tract infection, nasopharyngitis, rhinitis, sinusitis, pharyngitis, respiratory tract infection, and viral upper respiratory tract infection 150 Urinary tract infection122.3Metabolism and nutrition disorders Decreased appetite141.5Blood and lymphatic system disorders Anemia130.8Nervous system disorders Headache121.5Respiratory, thoracic and mediastinal disorders DyspneaComposite term includes dyspnea and dyspnea exertional 110Vascular disorders HypertensionComposite term includes hypertension and hypertensive crisis 114.5Table 5:Grade or Laboratory Abnormalities Worsening from Baseline in >= 1% of Patients with Advanced BCC Receiving LIBTAYO in Study 1620Laboratory AbnormalityGrade 3-4 (%)Percentages are based on the number of patients with at least post-baseline value available for that parameter Toxicity graded per NCI CTCAE v. 4.03Electrolytes Hyponatremia3.1 Hypokalemia1.5Coagulation Activated partial thromboplastin time prolonged2.3Hematology Lymphocyte count decreased2.3. Non-Small Cell Lung Cancer (NSCLC)The safety of LIBTAYO was evaluated in 355 patients with locally advanced or metastatic NSCLC in Study 1624 [see Clinical Studies (14.3)]. Patients received LIBTAYO 350 mg every weeks (n=355) or investigators choice of chemotherapy (n=342), consisting of paclitaxel plus cisplatin or carboplatin; gemcitabine plus cisplatin or carboplatin; or pemetrexed plus cisplatin or carboplatin followed by optional pemetrexed maintenance. The median duration of exposure was 27.3 weeks (9 days to 115 weeks) in the LIBTAYO group and 17.7 weeks (18 days to 86.7 weeks) in the chemotherapy group. In the LIBTAYO group, 54% of patients were exposed to LIBTAYO for >= months and 22 were exposed for >= 12 months.The safety population characteristics were: median age of 63 years (31 to 79 years), 44% of patients 65 or older, 88% male, 86%White, 82% had metastatic disease and 18% had locally advanced disease and ECOG performance score (PS) of (27%) and (73%).LIBTAYO was permanently discontinued due to adverse reactions in 6% of patients; adverse reactions resulting in permanent discontinuation in at least patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. Serious adverse reactions occurred in 28% of patients. The most frequent serious adverse reactions in at least 2% of patients were pneumonia and pneumonitis.Table summarizes the adverse reactions that occurred in >= 10% of patients and Table summarizes Grade or laboratory abnormalities in patients receiving LIBTAYO.Table 6: Adverse Reactions in >= 10% of Patients with Locally Advanced or Metastatic NSCLC Receiving LIBTAYO in Study 1624Adverse ReactionsLIBTAYON=355ChemotherapyN=342All Grades%Grades 3-4%All Grades%Grades 3-4%Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03Musculoskeletal and connective tissue disorders Musculoskeletal painMusculoskeletal pain is composite term that includes back pain, arthralgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, bone pain, myalgia, neck pain, spinal pain, and musculoskeletal stiffness 260.6271.5Skin and subcutaneous tissue disorders RashRash is composite term that includes rash, dermatitis, urticaria, rash maculo-papular, erythema, rash erythematous, rash pruritic, psoriasis, autoimmune dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, drug eruption, dyshidrotic eczema, lichen planus, and skin reaction 151.460Blood and lymphatic system disorders Anemia153.45016General disorders and administration site conditions FatigueFatigue is composite term that includes fatigue, asthenia, and malaise 141.1262Metabolism and nutrition disorders Decreased appetite120.6180.3Infections and infestations PneumoniaPneumonia is composite term that includes atypical pneumonia, embolic pneumonia, lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia bacterial, and pneumonia klebsiella 115125Respiratory, thoracic and mediastinal disorders CoughCough is composite term that includes cough and productive cough 11080.3Table 7: Grade or Laboratory Abnormalities Worsening from Baseline in >=1% of Patients with Locally Advanced or Metastatic NSCLC Receiving LIBTAYO in Study 1624Laboratory AbnormalityLIBTAYON=355ChemotherapyN=342Grades 3-4Percentages are based on the number of patients with at least post-baseline value available for that parameter. %Toxicity graded per NCI CTCAE v. 4.03Chemistry Increased aspartate aminotransferase3.91.2 Increased alanine aminotransferase2.70.3 Increased alkaline phosphatase2.40.3 Increased blood bilirubin2.10.3 Hypoalbuminemia1.81.3 Increased creatinine1.21.6Hematology Lymphopenia79 Anemia2.716Electrolytes Hyponatremia67 Hyperkalemia4.21.9 Hypocalcemia3.93.4 Hypophosphatemia2.44.1 Hypermagnesemia2.11.6 Hypokalemia1.52.2 Hypercalcemia1.22.2.

DOSAGE & ADMINISTRATION SECTION.

2DOSAGE AND ADMINISTRATION. The recommended dosage of LIBTAYO is 350 mg as an intravenous infusion over 30 minutes every weeks. (2.2). 2.1Patient Selection for NSCLC. Select patients with locally advanced or metastatic NSCLC for treatment with LIBTAYO based on PD-L1 expression on tumor cells [see Clinical Studies (14.3)]. Information on FDA-approved tests for the detection of PD-L1 expression is available at: http://www.fda.gov/CompanionDiagnostics.. 2.2Recommended Dosage. The recommended dosage of LIBTAYO is 350 mg administered as an intravenous infusion over 30 minutes every weeks until disease progression or unacceptable toxicity.. 2.3Dosage Modifications for Adverse Reactions No dose reduction for LIBTAYO is recommended. In general, withhold LIBTAYO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue LIBTAYO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.Dosage modifications for LIBTAYO for adverse reactions that require management different from these general guidelines are summarized in Table 1. Table 1: Recommended Dosage Modifications for Adverse Reactions Adverse ReactionSeverityBased on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 Dosage ModificationsALT=alanine aminotransferase, AST=aspartate aminotransferase, ULN=upper limit of normal, SJS=Stevens-Johnson Syndrome, TEN=toxic epidermal necrolysis, DRESS=Drug Rash with Eosinophilia and Systemic SymptomsImmune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)]Pneumonitis Grade 2WithholdResume in patients with complete or partial resolution (Grade to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids. Grades or 4Permanently discontinueColitisGrades or 3Withhold Grade 4Permanently discontinueHepatitis with no tumor involvement of the liverAST or ALT increases to more than and up to times ULN or Total bilirubin increases to more than 1.5 and up to times the ULNWithhold AST or ALT increases to more than times the ULN or Total bilirubin increases to more than times the ULNPermanently discontinueHepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue LIBTAYO based on recommendations for hepatitis with no liver involvement Baseline AST or ALT is more than and up to times ULN and increases to more than and up to 10 times ULN or Baseline AST or ALT is more than and up to times ULN and increases to more than and up to 10 times ULNWithhold AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than times ULNPermanently discontinueEndocrinopathiesGrades or 4Withhold until clinically stable or permanently discontinue depending on severityNephritis with Renal DysfunctionGrade or increased blood creatinineWithhold Grade increased blood creatininePermanently discontinueExfoliative Dermatologic ConditionsSuspected SJS, TEN, or DRESSWithhold Confirmed SJS, TEN, or DRESSPermanently discontinueMyocarditisGrade 2, or 4Permanently discontinueNeurological ToxicitiesGrade 2Withhold Grades or 4Permanently discontinueOther Adverse ReactionsInfusion-related reactions [see Warnings and Precautions (5.2)] Grade or 2Interrupt or slow the rate of infusionGrade or 4Permanently discontinue. 2.4Preparation and Administration. Visually inspect for particulate matter and discoloration prior to administration. LIBTAYO is clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles. Discard the vial if the solution is cloudy, discolored or contains extraneous particulate matter other than trace amounts of translucent to white particles.. Visually inspect for particulate matter and discoloration prior to administration. LIBTAYO is clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles. Discard the vial if the solution is cloudy, discolored or contains extraneous particulate matter other than trace amounts of translucent to white particles.. PreparationDo not shake.Withdraw mL from vial and dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between mg/mL to 20 mg/mL.Mix diluted solution by gentle inversion. Do not shake.Discard any unused medicinal product or waste material.. Do not shake.. Withdraw mL from vial and dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to final concentration between mg/mL to 20 mg/mL.. Mix diluted solution by gentle inversion. Do not shake.. Discard any unused medicinal product or waste material.. Storage of Infusion SolutionStore at room temperature up to 25C (77F) for no more than hours from the time of preparation to the end of the infusion or at 2C to 8C (36F to 46F) for no more than 24 hours from the time of preparation to the end of infusion.Allow the diluted solution to come to room temperature prior to administration.Do not freeze.. Store at room temperature up to 25C (77F) for no more than hours from the time of preparation to the end of the infusion or at 2C to 8C (36F to 46F) for no more than 24 hours from the time of preparation to the end of infusion.. Allow the diluted solution to come to room temperature prior to administration.. Do not freeze.. AdministrationAdminister by intravenous infusion over 30 minutes through an intravenous line containing sterile, in-line or add-on 0.2-micron to 5-micron filter.. Administer by intravenous infusion over 30 minutes through an intravenous line containing sterile, in-line or add-on 0.2-micron to 5-micron filter.

INDICATIONS & USAGE SECTION.

1INDICATIONS AND USAGE. LIBTAYO is programmed death receptor-1 (PD-1) blocking antibody indicated:Cutaneous Squamous Cell Carcinoma (CSCC)for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. (1.1)Basal Cell Carcinoma (BCC)for the treatment of patients with locally advanced BCC (laBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate. (1.2)for the treatment of patients with metastatic BCC (mBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate.1 (1.2) 1The mBCC indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit.Non-Small Cell Lung Cancer (NSCLC)for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) >= 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations, and is: locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic. (1.3, 2.1) for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. (1.1). for the treatment of patients with locally advanced BCC (laBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate. (1.2). for the treatment of patients with metastatic BCC (mBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate.1 (1.2) 1The mBCC indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit.. for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) >= 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations, and is: locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic. (1.3, 2.1) locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or. metastatic. (1.3, 2.1). 1.1Cutaneous Squamous Cell Carcinoma. LIBTAYO is indicated for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.. 1.2Basal Cell Carcinoma. LIBTAYO is indicated for the treatment of patients:with locally advanced basal cell carcinoma (laBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate.with metastatic BCC (mBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate. The mBCC indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for the mBCC indication may be contingent upon verification and description of clinical benefit.. with locally advanced basal cell carcinoma (laBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate.. with metastatic BCC (mBCC) previously treated with hedgehog pathway inhibitor or for whom hedgehog pathway inhibitor is not appropriate. The mBCC indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for the mBCC indication may be contingent upon verification and description of clinical benefit.. 1.3Non-Small Cell Lung Cancer. LIBTAYO is indicated for the first-line treatment of patients with non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) >= 50%] as determined by an FDA-approved test [see Dosage and Administration (2.1)]), with no EGFR, ALK or ROS1 aberrations, and is:locally advanced where patients are not candidates for surgical resection or definitive chemoradiation ormetastatic.. locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or. metastatic.

WARNINGS AND PRECAUTIONS SECTION.

5WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions (5.1)Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue LIBTAYO based on the severity of reaction. (2.3) Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue based on severity of reaction. (2.3, 5.2)Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with PD-1/PD-L1 blocking antibody. (5.3)Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to fetus and use of effective contraception. (5.4, 8.1, 8.3). Immune-Mediated Adverse Reactions (5.1)Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue LIBTAYO based on the severity of reaction. (2.3) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue LIBTAYO based on the severity of reaction. (2.3). Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue based on severity of reaction. (2.3, 5.2). Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with PD-1/PD-L1 blocking antibody. (5.3). Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to fetus and use of effective contraception. (5.4, 8.1, 8.3). 5.1Severe and Fatal Immune-Mediated Adverse Reactions. LIBTAYO is monoclonal antibody that belongs to class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions.Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting PD-1/PD-L1 blocking antibody. 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.Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.Withhold or permanently discontinue LIBTAYO depending on severity [see Dosage and Administration (2.3)]. In general, if LIBTAYO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to mg/kg/day prednisone or equivalent) until improvement to Grade or less. Upon improvement to Grade or less, initiate corticosteroid taper and continue to taper over at least month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.. Immune-Mediated PneumonitisLIBTAYO can cause immune-mediated pneumonitis. The definition of immune-mediated pneumonitis included the required use of systemic corticosteroids or other immunosuppressants and the absence of clear alternate etiology. In patients treated with other PD-1/PD-L1 blocking antibodies the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.Immune-mediated pneumonitis occurred in 3.2% (26/810) of patients receiving LIBTAYO, including Grade (0.5%), Grade (0.5%), and Grade (2.1%) adverse reactions. Pneumonitis led to permanent discontinuation of LIBTAYO in 1.4% of patients and withholding of LIBTAYO in 2.1% of the patients.Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in 58% of the 26 patients. Of the 17 patients in whom LIBTAYO was withheld for pneumonitis, reinitiated LIBTAYO after symptom improvement; of these, 3/9 (33%) had recurrence of pneumonitis.. Immune-Mediated ColitisLIBTAYO can cause immune-mediated colitis. The definition of immune-mediated colitis included the required use of systemic corticosteroids or other immunosuppressants and the absence of clear alternate etiology. The primary component of the immune-mediated colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.Immune-mediated colitis occurred in 2.2% (18/810) of patients receiving LIBTAYO, including Grade (0.9%) and Grade (1.1%) adverse reactions. Colitis led to permanent discontinuation of LIBTAYO in 0.4% of patients and withholding of LIBTAYO in 1.5% of patients.Systemic corticosteroids were required in all patients with colitis. Colitis resolved in 39% of the 18 patients. Of the 12 patients in whom LIBTAYO was withheld for colitis, reinitiated LIBTAYO after symptom improvement; of these, 3/4 (75%) had recurrence of colitis.. Immune-Mediated HepatitisLIBTAYO can cause immune-mediated hepatitis. The definition of immune-mediated hepatitis included the required use of systemic corticosteroids or other immunosuppressants and the absence of clear alternate etiology.Immune-mediated hepatitis occurred in 2% (16/810) of patients receiving LIBTAYO, including fatal (0.1%), Grade (0.1%), Grade (1.4%), and Grade (0.2%) adverse reactions. Hepatitis led to permanent discontinuation of LIBTAYO in 1.2% of patients and withholding of LIBTAYO in 0.5% of patients.Systemic corticosteroids were required in all patients with hepatitis. Nineteen percent (19%) of these patients (3/16) required additional immunosuppression with mycophenolate. Hepatitis resolved in 50% of the 16 patients. Of the patients in whom LIBTAYO was withheld for hepatitis, patients reinitiated LIBTAYO after symptom improvement; of these, none had recurrence of hepatitis.. Immune-Mediated Endocrinopathies. Adrenal InsufficiencyLIBTAYO can cause primary or secondary adrenal insufficiency. For Grade or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold LIBTAYO depending on severity [see Dosage and Administration (2.3)].Adrenal insufficiency occurred in 0.4% (3/810) of patients receiving LIBTAYO, including Grade (0.4%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of LIBTAYO in (0.1%) patient. LIBTAYO was not withheld in any patient due to adrenal insufficiency. Systemic corticosteroids were required in all patients with adrenal insufficiency; of these 67% (2/3) remained on systemic corticosteroids. Adrenal insufficiency had not resolved in any patient at the time of data cutoff.. HypophysitisLIBTAYO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue LIBTAYO depending on severity [see Dosage and Administration (2.3)]. Hypophysitis occurred in 0.4% (3/810) of patients receiving LIBTAYO, including Grade (0.2%) and Grade (0.1%) adverse reactions. Hypophysitis led to permanent discontinuation of LIBTAYO in (0.1%) patient and withholding of LIBTAYO in (0.1%) patient. Systemic corticosteroids were required in 67% (2/3) patients with hypophysitis. Hypophysitis had not resolved in any patient at the time of data cutoff.. Thyroid DisordersLIBTAYO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue LIBTAYO depending on severity [see Dosage and Administration (2.3)].. Thyroiditis: Thyroiditis occurred in 0.6% (5/810) of patients receiving LIBTAYO, including Grade (0.2%) adverse reactions. No patient discontinued LIBTAYO due to thyroiditis. Thyroiditis led to withholding of LIBTAYO in patient. Systemic corticosteroids were not required in any patient with thyroiditis. Thyroiditis had not resolved in any patient at the time of data cutoff.Blood thyroid stimulating hormone increased and blood thyroid stimulating hormone decreased have also been reported.. Hyperthyroidism: Hyperthyroidism occurred in 3.2% (26/810) of patients receiving LIBTAYO, including Grade (0.9%) adverse reactions. No patient discontinued treatment due to hyperthyroidism. Hyperthyroidism led to withholding of LIBTAYO in 0.5% of patients.Systemic corticosteroids were required in 3.8% (1/26) of patients with hyperthyroidism. Hyperthyroidism resolved in 50% of the 26 patients. Of the patients in whom LIBTAYO was withheld for hyperthyroidism, patients reinitiated LIBTAYO after symptom improvement; of these, none had recurrence of hyperthyroidism.. Hypothyroidism: Hypothyroidism occurred in 7% (60/810) of patients receiving LIBTAYO, including Grade (6%) adverse reactions. Hypothyroidism led to permanent discontinuation of LIBTAYO in (0.1%) patient. Hypothyroidism led to withholding of LIBTAYO in 1.1% of patients.Systemic corticosteroids were not required in any patient with hypothyroidism. Hypothyroidism resolved in 8.3% of the 60 patients. The majority of patients with hypothyroidism required long-term thyroid hormone replacement.Of the patients in whom LIBTAYO was withheld for hypothyroidism, reinitiated LIBTAYO after symptom improvement; required ongoing hormone replacement therapy.. Type Diabetes Mellitus, which can present with diabetic ketoacidosis.Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold LIBTAYO depending on severity [see Dosage and Administration (2.3)].Type diabetes mellitus occurred in 0.1% (1/810) of patients, including Grade (0.1%) adverse reactions. No patient discontinued treatment due to Type diabetes mellitus. Type diabetes mellitus led to withholding of LIBTAYO in 0.1% of patients.. Immune-Mediated Nephritis with Renal DysfunctionLIBTAYO can cause immune-mediated nephritis. The definition of immune-mediated nephritis included the required use of systemic corticosteroids or other immunosuppressants and the absence of clear alternate etiology.Immune-mediated nephritis occurred in 0.6% (5/810) patients receiving LIBTAYO, including fatal (0.1%), Grade (0.1%) and Grade (0.4%) adverse reactions. Nephritis led to permanent discontinuation of LIBTAYO in 0.1% of patients and withholding of LIBTAYO in 0.4% of patients.Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in 80% of the patients. Of the patients in whom LIBTAYO was withheld for nephritis, reinitiated LIBTAYO after symptom improvement; of these, none had recurrence of nephritis.. Immune-Mediated Dermatologic Adverse ReactionsLIBTAYO can cause immune-mediated rash or dermatitis. The definition of immune-mediated dermatologic adverse reaction included the required use of systemic corticosteroids or other immunosuppressants and the absence of clear alternate etiology. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue LIBTAYO depending on severity [see Dosage and Administration (2.3)].Immune-mediated dermatologic adverse reactions occurred in 1.6% (13/810) of patients receiving LIBTAYO, including Grade (0.9%) and Grade (0.6%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of LIBTAYO in 0.1% of patients and withholding of LIBTAYO in 1.4% of patients.Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 69% of the 13 patients. Of the 11 patients in whom LIBTAYO was withheld for dermatologic adverse reaction, reinitiated LIBTAYO after symptom improvement; of these 43% (3/7) had recurrence of the dermatologic adverse reaction.. Other Immune-Mediated Adverse ReactionsThe following clinically significant immune-mediated adverse reactions occurred at an incidence of 1% in 810 patients who received LIBTAYO or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis. Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider Vogt-Koyanagi-Harada like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.. Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis, stomatitis. Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica. Endocrine: Hypoparathyroidism. 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. 5.2Infusion-Related Reactions. Severe infusion-related reactions (Grade 3) occurred in 0.1% of patients receiving LIBTAYO as 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)].. 5.3Complications of Allogeneic HSCT. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with 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 PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.. 5.4Embryo-Fetal Toxicity. Based on its mechanism of action, LIBTAYO can cause fetal harm when administered to pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to fetus. Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least months after the last dose [see Use in Specific Populations (8.1, 8.3)].