Libtayo Drug Information

Patient Selection for NSCLC

Select patients with locally advanced or metastatic NSCLC for treatment with LIBTAYO as a single agent based on PD-L1 expression on tumor cells. Information on FDA-approved tests for the detection of PD-L1 expression is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended dosages of LIBTAYO are presented in Table 1. Refer to the Prescribing Information for the agents administered in combination with LIBTAYO for recommended dosing information, as appropriate. Table 1: Recommended Dosages of LIBTAYO as a Single Agent or in Combination with Other Agents s 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 2.

Table 2: Recommended

Preparation and Administration

Visually inspect for particulate matter and discoloration prior to administration. LIBTAYO is a 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.

Preparation Do not shake the vial(s). Withdraw the required volume from the vial(s) of LIBTAYO and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 1 mg/mL to 20 mg/mL. Mix diluted solution by gentle inversion.

Do not shake. Discard any unused portion left in the vial(s). Storage of Diluted Solution Store at room temperature up to 25°C (77°F) for no more than 8 hours from the time of preparation to the end of the infusion or under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 10 days 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. Administration Administer by intravenous infusion over 30 minutes through an intravenous line containing a sterile, in-line or add-on 0.2-micron to 5-micron filter.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in Warnings and Precautions reflect exposure to LIBTAYO as a single agent in 1281 patients with advanced cancers in three open-label, single-arm, multicohort studies, and two open-label randomized multi-center studies. These studies included 24, and 404 patients with other advanced solid tumors.

In this pooled safety population, the most common adverse reactions (≥15%) were fatigue, musculoskeletal pain, rash, diarrhea, and anemia. The most common Grade 3-4 laboratory abnormalities (≥2%) were lymphopenia, anemia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, hypokalemia, hyperkalemia, and increased alanine aminotransferase. Cutaneous Squamous Cell Carcinoma (CSCC) Study 1540 The safety of LIBTAYO was evaluated in 358 patients with advanced CSCC (metastatic or locally advanced disease) in Study as an intravenous infusion until disease progression, unacceptable toxicity, or completion of planned treatment.

The median duration of exposure was 40 weeks (1 week to 109 weeks). Serious adverse reactions occurred in 41% of patients. Fatal adverse reactions occurred in 5% of patients who received LIBTAYO, including deaths due to infections (2.2%).

Permanent discontinuation due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation in at least 2 patients were pneumonitis, rash, confusional state, general physical health deterioration, hemorrhage, liver function test abnormalities, and musculoskeletal pain. Dosage interruptions of LIBTAYO due to an adverse reaction occurred in 36% of patients.

Adverse reactions which required dosage interruption in ≥2% of patients included diarrhea, infusion-related reaction, upper respiratory tract infection, liver function test abnormalities, musculoskeletal pain, pneumonitis, and rash. The most common (≥20%) adverse reactions were fatigue, rash, musculoskeletal pain, diarrhea, pruritus, and nausea. The most common Grade 3 or 4 adverse reactions (≥2%) were hypertension, skin infection, pneumonia, anemia, fatigue, musculoskeletal pain, and pneumonitis.

The most common (≥4%) Grade 3 or 4 laboratory abnormalities worsening from baseline were lymphopenia, hyponatremia, anemia, and hypophosphatemia. Adjuvant treatment of CSCC at high risk of recurrence C-POST study The safety of LIBTAYO was evaluated in patients with CSCC at high-risk of recurrence after surgery and radiation in the C-POST study. Treatment continued until disease recurrence, unacceptable toxicity, or up to 48 weeks.

The median duration of exposure was 48 weeks (range: 3 weeks to 52 weeks) in LIBTAYO-treated patients. Serious adverse reactions occurred in 18% of patients who received LIBTAYO. Adverse reactions resulting in permanent discontinuation in ≥1% of patients were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, and adrenal insufficiency.

Adverse reactions leading to interruptions in ≥1% of patients included COVID-19, diarrhea, alanine aminotransferase increased, urinary tract infection, upper respiratory tract infection, aspartate aminotransferase increased, edema, dyspnea, pneumonitis, pneumonia, and rash. Table 5: Adverse Reactions in ≥10% of Patients with CSCC at High Risk of Recurrence in the Adjuvant Setting Receiving LIBTAYO with a Difference Between Arms of ≥3% Compared to 0 Table 6: Laboratory Abnormalities Worsening from Baseline in ≥1% of Patients with CSCC at High Risk of Recurrence in the Adjuvant Setting Receiving Basal Cell Carcinoma (BCC) The safety of LIBTAYO was evaluated in 138 patients with advanced BCC (mBCC N=54, laBCC N=84) in an open-label, single-arm trial (Study 1620). Patients received LIBTAYO 350 mg every 3 weeks as an intravenous infusion for up to 93 weeks or until disease progression or unacceptable toxicity.

The median duration of exposure was 45 weeks (range: 2.1 weeks to 98 weeks). Serious adverse reactions occurred in 34% of patients. Fatal adverse reactions occurred in 4.3% of patients who received LIBTAYO, including acute kidney injury (0.7%) and cachexia worsening due to colitis (0.7%).

Adverse reactions resulting in permanent discontinuation of LIBTAYO in at least 2 patients were diarrhea, acute kidney injury, general physical health deterioration, and hepatitis. Adverse reactions which required dosage interruptions in > 2% of patients included diarrhea, musculoskeletal pain, acute kidney injury, fatigue, fall, headache, infusion-related reaction, hemorrhage, pneumonitis, upper respiratory tract infection, and urinary tract infection. The most common adverse reactions reported in at least 15% of patients were fatigue, musculoskeletal pain, diarrhea, rash, upper respiratory tract infection, pruritus, hemorrhage, and hypertension.

The most common Grade 3 or 4 adverse reactions (> 2%) were hypertension, diarrhea, fatigue, musculoskeletal pain, hypokalemia, hyponatremia, pneumonia, urinary tract infection, visual impairment, and weight decreased. The most common (> 2%) laboratory abnormalities worsening from baseline to Grade 3 or 4 were lymphopenia and hyponatremia. Table 7: Adverse Reactions in ≥10% of Patients with Advanced BCC Receiving Table 8: Grade 3 or 4 Laboratory Abnormalities Worsening from Baseline in ≥1% of Patients with Advanced BCC Receiving Non-Small Cell Lung Cancer (NSCLC) First-line treatment of NSCLC with LIBTAYO in Combination with Platinum-based Chemotherapy The safety of LIBTAYO in combination with platinum-based chemotherapy was evaluated in 465 patients with locally advanced or metastatic NSCLC in Study 16113.

Among patients who received LIBTAYO, 70% were exposed for 6 months or longer and 35% were exposed for greater than one year. Serious adverse reactions occurred in 25% of patients. The most frequent serious adverse reactions that occurred in at least 2% of patients were pneumonia, anemia, and neutropenia.

Fatal adverse reactions occurred in 6% of patients who received LIBTAYO in combination with chemotherapy, including death not otherwise specified (2.9%), sudden death (1.0%), acute hepatitis (0.3%), acute respiratory distress syndrome was permanently discontinued due to adverse reactions in 5% of patients. Adverse reactions resulting in permanent discontinuation in at least 2 patients were increased alanine aminotransferase and anemia. Adverse reactions which required dosage interruptions in at least 2% of patients were anemia, pneumonia, neutropenia, thrombocytopenia, fatigue, COVID-19 infection, and pyrexia.

The most common (≥15%) adverse reactions were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite. Patients received LIBTAYO 350 mg every 3 weeks (n=355) or investigator's 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. LIBTAYO was permanently discontinued due to adverse reactions in 6% of patients; adverse reactions resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke, and increased aspartate aminotransferase.

Serious adverse reactions occurred in 28% of patients.

Pregnancy Risk Summary Based on its mechanism of action, LIBTAYO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LIBTAYO in pregnant women. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death (see Data ).

Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, LIBTAYO has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data Animal reproduction studies have not been conducted with LIBTAYO to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering LIBTAYO during pregnancy include increased rates of abortion or stillbirth.

As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to cemiplimab-rwlc may increase the risk of developing immune-mediated disorders or altering the normal immune response.

Pediatric Use The safety and effectiveness of LIBTAYO have not been established in pediatric patients. The safety and efficacy of LIBTAYO as a single agent (Part 1, N=25) or in combination with radiation therapy (Part 2, N=22) were evaluated but not established in a two-part, open-label, multi-center trial (Study 1690, NCT03690869) in pediatric patients (birth to < 17 years) with relapsed or refractory solid tumors (Part 1) or relapsed or refractory CNS tumors (Parts 1 and 2) or newly diagnosed CNS tumors (Part 2). No new safety signals were observed in these pediatric patients.

Cemiplimab exposure in 46 pediatric patients aged 1 to < 17 years was within the range of values previously observed in adults given a similar dose based on body weight.