Bavencio

avelumab · Injection, Solution, Concentrate · Intravenous

Prescription (Rx) Programmed Death Ligand-1 Blocker

Uses

1 INDICATIONS AND USAGE BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for: Merkel Cell Carcinoma (MCC) Adults and pediatric patients 12 years and older with metastatic MCC. ( 1.1 , 14.1 ) Urothelial Carcinoma (UC) Maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy. ( 1.2 , 14.2 ) Patients with locally advanced or metastatic UC who: Have disease progression during or following platinum-containing chemotherapy. ( 1.2 , 14.2 ) Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. ( 1.2 , 14.2 ) Renal Cell Carcinoma (RCC) First-line treatment, in combination with axitinib, of patients with advanced RCC. ( 1.3 , 14.3 ) 1.1 Metastatic Merkel Cell Carcinoma BAVENCIO (avelumab) is indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC) [see Clinical Studies (14.1) ] . 1.2 Locally Advanced or Metastatic Urothelial Carcinoma First-Line Maintenance Treatment of Urothelial Carcinoma BAVENCIO is indicated for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy [see Clinical Studies (14.2) ] . Previously-treated Urothelial Carcinoma BAVENCIO is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who: Have disease progression during or following platinum-containing chemotherapy Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy [see Clinical Studies (14.2) ]. 1.3 Advanced Renal Cell Carcinoma BAVENCIO in combination with axitinib is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC) [see Clinical Studies (14.3) ] .

Dosage and administration

Premedicate for the first 4 infusions and subsequently as needed. ( 2.1 ) Merkel Cell Carcinoma : 800 mg every 2 weeks. ( 2.2 ) Urothelial Carcinoma ; 800 mg every 2 weeks. ( 2.3 ) Renal Cell Carcinoma : 800 mg every 2 weeks in combination with axitinib 5 mg orally twice daily. ( 2.4 ) Administer BAVENCIO as an intravenous infusion over 60 minutes. 2.1 Premedication Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions of BAVENCIO. Premedication should be administered for subsequent BAVENCIO doses based upon clinical judgment and presence/severity of prior infusion reactions [see Dosage and Administration (2.5) and Warnings and Precautions (5.2) ]. 2.2 Recommended Dosage for MCC The recommended dosage of BAVENCIO is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. 2.3 Recommended Dosage for UC The recommended dosage of BAVENCIO is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. 2.4 Recommended Dosage for RCC The recommended dosage of BAVENCIO is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks in combination with axitinib 5 mg orally taken twice daily (12 hours apart) with or without food until disease progression or unacceptable toxicity. When axitinib is used in combination with BAVENCIO, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of two weeks or longer. Review the Full Prescribing Information for axitinib prior to initiation. 2.5 Dose Modifications No dose reduction for BAVENCIO is recommended. In general, withhold BAVENCIO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue BAVENCIO 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 or equivalent per day within 12 weeks of initiating corticosteroids. Dosage modifications for BAVENCIO for adverse reactions that require management different from these general guidelines are summarized in Table 1. Table 1: Recommended Monotherapy Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 Dosage Modification ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal, SJS = Stevens-Johnson syndrome, TEN = toxic epidermal necrosis, DRESS = drug rash with eosinophilia and systemic symptoms Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating corticosteroids. Grade 3 or 4 Permanently discontinue Colitis Grade 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver For liver enzyme elevations in patients treated with combination therapy, see Table 2 AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue BAVENCIO based on recommendations for hepatitis where there is no tumor involvement of the liver. Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grade 3 or 4 Withhold until clinically stable or permanently discontinue depending on severity Nephritis with Renal Dysfunction Grade 2 or 3 increased blood creatinine Withhold Grade 4 increased blood creatinine Permanently discontinue Exfoliative Dermatologic Conditions Suspected SJS, TEN, or DRESS Withhold Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grade 2, 3 or 4 Permanently discontinue Neurological Toxicities Grade 2 Withhold Grade 3 or 4 Permanently discontinue Other Adverse Reactions Infusion-related reactions [see Warnings and Precautions (5.2) ] Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Permanently discontinue Table 2 presents dosage modifications that are different from those described above in Table 1 for BAVENCIO used as monotherapy or in the Full Prescribing Information for the drug administered in combination. Table 2: Recommended Specific Dosage Modifications for Adverse Reactions for Combination Therapy [see Warnings and Precautions (5.1) ] Treatment Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 Dosage Modification BAVENCIO in combination with axitinib Liver enzyme elevations ALT or AST at least 3 times ULN but less than 10 times ULN without concurrent total bilirubin at least 2 times ULN Withhold both BAVENCIO and axitinib until adverse reactions recover to Grades 0-1 Consider corticosteroid therapy Consider rechallenge with BAVENCIO or axitinib or sequential rechallenge with both BAVENCIO and axitinib after recovery Dose reduction according to the axitinib Full Prescribing Information should be considered if rechallenging with axitinib.

Dosage forms and strengths

Injection: 200 mg/10 mL (20 mg/mL), clear, colorless to slightly yellow solution in a single-dose vial. Injection: 200 mg/10 mL (20 mg/mL) solution in single-dose vial. ( 3 )

Contraindications

None. None. ( 4 )

Warnings 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 nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and may result in 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 based on severity and type of reaction. Infusion-related reactions : Interrupt, slow the rate of infusion, or permanently discontinue BAVENCIO based on severity of reaction. ( 5.2 ) Complications of allogeneic HSCT : Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. ( 5.3 ) Major adverse cardiovascular events : Optimize management of cardiovascular risk factors. Discontinue BAVENCIO in combination with axitinib for Grade 3-4 events. ( 5.4 ) Embryo-fetal toxicity : BAVENCIO can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions BAVENCIO is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (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 treatment with a 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. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients 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 BAVENCIO depending on severity [see Dosage and Administration (2.5) ]. In general, if BAVENCIO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic corticosteroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis BAVENCIO can cause immune-mediated pneumonitis. Immune-mediated pneumonitis occurred in 1.1% (21/1854) of patients receiving BAVENCIO, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (0.3%) and Grade 2 (0.6%) adverse reactions. Pneumonitis led to permanent discontinuation of BAVENCIO in 0.3% and withholding of BAVENCIO in 0.3% of patients. Systemic corticosteroids were required in all (21/21) patients with pneumonitis. Pneumonitis resolved in 57% (12/21) of the patients. Of the 5 patients in whom BAVENCIO was withheld for pneumonitis, 5 reinitiated treatment with BAVENCIO after symptom improvement; of these, none had recurrence of pneumonitis. With other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-Mediated Colitis BAVENCIO can cause immune-mediated colitis. The primary component of the immune-mediated colitis consisted of diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.5% (27/1854) of patients receiving BAVENCIO, including Grade 3 (0.4%) and Grade 2 (0.8%) adverse reactions. Colitis led to permanent discontinuation of BAVENCIO in 0.5% and withholding of BAVENCIO in 0.4% of patients. Systemic corticosteroids were required in all (27/27) patients with colitis. Colitis resolved in 70% (19/27) of the patients. Of the 8 patients in whom BAVENCIO was withheld for colitis, 5 reinitiated treatment with BAVENCIO after symptom improvement; of these, 40% had recurrence of colitis. Hepatotoxicity and Immune-Mediated Hepatitis BAVENCIO as a single agent BAVENCIO can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.1% (20/1854) of patients receiving BAVENCIO, including fatal (0.1%), Grade 3 (0.8%), and Grade 2 (0.2%) adverse reactions. Hepatitis led to permanent discontinuation of BAVENCIO in 0.6% and withholding of BAVENCIO in 0.2% of patients. Systemic corticosteroids were required in all (20/20) patients with hepatitis. Hepatitis resolved in 60% (12/20) of the patients.

Side effects

The following clinically significant 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) ] Major adverse cardiovascular events [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥ 20%) in patients were: MCC : Fatigue, musculoskeletal pain, infusion-related reaction, rash, nausea, constipation, cough, and diarrhea. ( 6.1 ) UC : Maintenance treatment: fatigue, musculoskeletal pain, urinary tract infection, and rash. ( 6.1 ) Previously-treated: fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection. ( 6.1 ) RCC (with axitinib) : diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 the WARNINGS AND PRECAUTIONS section reflect exposure to BAVENCIO 10 mg/kg intravenously every 2 weeks as a single agent in 1854 patients enrolled in the JAVELIN Merkel 200 and JAVELIN Solid Tumor trials and to BAVENCIO 10 mg/kg intravenously every 2 weeks in combination with axitinib 5 mg orally twice daily in 489 patients enrolled in the JAVELIN Renal 100 and JAVELIN Renal 101 trials. In the BAVENCIO monotherapy population, 25% of patients were exposed for ≥ 6 months and 9% were exposed for ≥ 12 months. The population characteristics of BAVENCIO in combination with axitinib are shown below. When BAVENCIO was used in combination with axitinib, 70% of patients were exposed for ≥ 6 months and 31% were exposed for ≥ 12 months. The following criteria were used to classify an adverse reaction as immune-mediated: onset within 90 days after last dose of BAVENCIO, no spontaneous resolution within 7 days of onset, treatment with corticosteroids or other immunosuppressant or hormone replacement therapy, biopsy consistent with immune-mediated reaction, and no other clear etiology. Metastatic Merkel Cell Carcinoma The safety of BAVENCIO was evaluated in 204 patients enrolled in the JAVELIN Merkel 200 trial with metastatic MCC. Patients received BAVENCIO 10 mg/kg intravenously every 2 weeks or 800 mg intravenously every 2 weeks until disease progression or unacceptable toxicity. The median duration of exposure to BAVENCIO was 4.1 months (range: 2 weeks to 48 months). [see Clinical Studies (14.1) ] . Serious adverse reactions occurred in 52% of patients receiving BAVENCIO. The most frequent serious adverse reactions (≥ 2% of patients) were general physical health deterioration, anemia, abdominal pain, acute kidney injury, sepsis, hyponatremia, and infusion-related reaction. Permanent discontinuation of BAVENCIO due to an adverse reaction occurred in 27% of patients. The most frequent adverse reactions (> 1% of patients) that resulted in permanent discontinuation were infusion-related reaction, anemia, increased ALT, and increased AST. Dosage interruptions of BAVENCIO due to an adverse reaction, excluding temporary interruptions due to infusion-related reactions, occurred in 29% of patients. The most frequent adverse reactions (> 1% of patients) that required dosage interruption were nasopharyngitis, anemia, diarrhea, lung infection, and ALT increased. The most common adverse reactions (≥ 20%) that occurred in patients receiving BAVENCIO were fatigue, musculoskeletal pain, infusion-related reaction, rash, nausea, constipation, cough, and diarrhea. Table 3 and Table 4 summarize the adverse reactions and laboratory abnormalities, respectively, that occurred in patients receiving BAVENCIO. Table 3: Adverse Reactions in ≥ 10% of Patients with Metastatic MCC Receiving BAVENCIO in the JAVELIN Merkel 200 Trial Adverse Reactions BAVENCIO (N=204) All Grades % Grade 3-4 % General Disorders Fatigue Includes fatigue and asthenia. 47 2.9 Infusion-related reaction Includes infusion-related reaction, chills, pyrexia, back pain, hypotension, drug hypersensitivity, dyspnea, flushing and hypersensitivity. 26 0.5 Edema Includes peripheral edema, peripheral swelling, and genital edema. 17 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Includes musculoskeletal pain, back pain, pain in extremity, myalgia, musculoskeletal pain, and neck pain. 29 1.5 Arthralgia 13 0.5 Skin and Subcutaneous Tissue Disorders Rash Includes rash, erythema, rash maculo-papular, rash pruritic, dermatitis bullous, rash erythematous, and rash macular. 25 0 Pruritus Includes pruritus and pruritus generalized. 16 0.5 Gastrointestinal Disorders Nausea 23 0 Constipation 22 0.5 Diarrhea Includes diarrhea and colitis. 21 1 Abdominal pain Includes abdominal pain, abdominal pain upper, and abdominal pain lower. 16 3.4 Vomiting 12 1 Respiratory, Thoracic and Mediastinal Disorders Cough 22 0 Dyspnea Includes dyspnea and dyspnea exertional. 15 1 Metabolism and Nutrition Disorders Decreased appetite 18 3.4 Decreased weight 16 0.5 Vascular Disorders Hypertension 11 6 Other clinically significant adverse reactions in < 10% of patients receiving BAVENCIO in the JAVELIN Merkel 200 trial were dizziness, headache, transaminase increased, creatine phosphokinase increased, and tubulointerstitial nephritis.

Use in specific populations

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of BAVENCIO in pregnant women [see Clinical Pharmacology (12.1) ] . 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 IgG1 immunoglobulins (IgG1) are known to cross the placenta. Therefore, BAVENCIO has the potential to be transmitted from the mother to the developing fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient 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 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with BAVENCIO 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 BAVENCIO 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 BAVENCIO may increase the risk of developing immune-mediated disorders or altering the normal immune response. 8.2 Lactation Risk Summary There is no information regarding the presence of avelumab in human milk, the effects on the breastfed infant, or the effects on milk production. Since many drugs including antibodies are excreted in human milk, advise a lactating woman not to breastfeed during treatment and for at least one month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants. 8.3 Females and Males of Reproductive Potential Contraception Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. 8.4 Pediatric Use The safety and effectiveness of BAVENCIO have been established in pediatric patients aged 12 years and older for metastatic MCC. Use of BAVENCIO in this age group is supported by evidence from adequate and well-controlled studies of BAVENCIO in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the steady state exposure of avelumab, that drug exposure is generally similar between adults and pediatric patients age 12 years and older for monoclonal antibodies, and that the course of MCC is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The recommended dose in pediatric patients 12 years of age or greater is the same as that in adults [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . Safety and effectiveness of BAVENCIO have not been established in pediatric patients less than 12 years of age. 8.5 Geriatric Use Metastatic Merkel Cell Carcinoma Of the 204 patients with MCC who received BAVENCIO in the JAVELIN Merkel 200 trial, 78% were 65 years or older and 43% were 75 years or older. No overall differences in safety or efficacy were observed between elderly patients and younger patients. Locally Advanced or Metastatic Urothelial Carcinoma Of the 344 patients randomized to BAVENCIO 10 mg/kg plus BSC in the JAVELIN Bladder 100 trial, 63% were 65 years or older and 24% were 75 years or older. No overall differences in safety or efficacy were reported between elderly patients and younger patients. Advanced Renal Cell Carcinoma Of the 434 patients randomized to BAVENCIO 10 mg/kg administered in combination with axitinib 5 mg twice daily in the JAVELIN Renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. No overall difference in safety or efficacy were reported between elderly patients and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary Based on its mechanism of action, BAVENCIO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of BAVENCIO in pregnant women [see Clinical Pharmacology (12.1) ] . 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 IgG1 immunoglobulins (IgG1) are known to cross the placenta. Therefore, BAVENCIO has the potential to be transmitted from the mother to the developing fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient 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 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with BAVENCIO 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 BAVENCIO 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 BAVENCIO may increase the risk of developing immune-mediated disorders or altering the normal immune response.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of BAVENCIO have been established in pediatric patients aged 12 years and older for metastatic MCC. Use of BAVENCIO in this age group is supported by evidence from adequate and well-controlled studies of BAVENCIO in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the steady state exposure of avelumab, that drug exposure is generally similar between adults and pediatric patients age 12 years and older for monoclonal antibodies, and that the course of MCC is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The recommended dose in pediatric patients 12 years of age or greater is the same as that in adults [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . Safety and effectiveness of BAVENCIO have not been established in pediatric patients less than 12 years of age.

Geriatric use

8.5 Geriatric Use Metastatic Merkel Cell Carcinoma Of the 204 patients with MCC who received BAVENCIO in the JAVELIN Merkel 200 trial, 78% were 65 years or older and 43% were 75 years or older. No overall differences in safety or efficacy were observed between elderly patients and younger patients. Locally Advanced or Metastatic Urothelial Carcinoma Of the 344 patients randomized to BAVENCIO 10 mg/kg plus BSC in the JAVELIN Bladder 100 trial, 63% were 65 years or older and 24% were 75 years or older. No overall differences in safety or efficacy were reported between elderly patients and younger patients. Advanced Renal Cell Carcinoma Of the 434 patients randomized to BAVENCIO 10 mg/kg administered in combination with axitinib 5 mg twice daily in the JAVELIN Renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. No overall difference in safety or efficacy were reported between elderly patients and younger patients.

Description

Avelumab is a programmed death ligand1 (PD-L1) blocking antibody. Avelumab is a human IgG1 lambda monoclonal antibody produced in Chinese hamster ovary cells and has a molecular weight of approximately 147 kDa. BAVENCIO (avelumab) Injection for intravenous use is a sterile, preservative-free, non-pyrogenic, clear, colorless to slightly yellow solution. Each single-dose vial contains 200 mg avelumab in 10 mL (20 mg/mL). Each mL contains 20 mg avelumab, D-mannitol (51 mg), glacial acetic acid (0.6 mg), polysorbate 20 (0.5 mg), sodium hydroxide (0.3 mg), and Water for Injection. The pH range of the solution is 5.0 – 5.6.

Mechanism of action

12.1 Mechanism of Action PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production. Avelumab binds PD-L1 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

How supplied

(avelumab) Injection is a sterile, preservative-free, and clear, colorless to slightly yellow solution for intravenous infusion supplied as a single-dose vial of 200 mg/10 mL (20 mg/mL), individually packed into a carton (NDC 44087-3535-1). Store refrigerated at 36°F to 46°F (2°C to 8°C) in original package to protect from light. Do not freeze or shake the vial. The vial stopper is not made with natural rubber latex.

Storage

Store refrigerated at 36°F to 46°F (2°C to 8°C) in original package to protect from light. Do not freeze or shake the vial. The vial stopper is not made with natural rubber latex.

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune-Mediated Adverse Reactions Inform patients of the risk of immune-mediated adverse reactions requiring corticosteroids or hormone replacement therapy, including, but not limited to: Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1) ]. Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1) ] . Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding [see Warnings and Precautions (5.1) ] . Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypothyroidism, hyperthyroidism, and diabetes mellitus [see Warnings and Precautions (5.1) ] . Nephritis with Renal Dysfunction: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis including decreased urine output, blood in urine, swelling in ankles, loss of appetite, and any other symptoms of renal dysfunction [see Warnings and Precautions (5.1) ] . Dermatologic Adverse Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of skin rash, itchy skin, rash with tiny spots and bumps, reddening of skin, blisters or peeling [see Warnings and Precautions (5.1) ] . Infusion-Related Reactions Advise patients to contact their healthcare provider immediately for signs or symptoms of potential infusion-related reactions [see Warnings and Precautions (5.2) ] . Complications of Allogeneic HSCT Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3) ] . Major Adverse Cardiovascular Events Advise patients receiving BAVENCIO in combination with axitinib to contact their healthcare provider immediately for signs or symptoms of cardiovascular events including but not limited to new or worsening chest discomfort, dyspnea, or peripheral edema [see Warnings and Precautions (5.4) ]. Embryo-Fetal Toxicity Advise females of reproductive potential that BAVENCIO can cause fetal harm. Instruct females of reproductive potential to use effective contraception during and for at least one month after the last dose of BAVENCIO [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1 , 8.3) ] . Lactation Advise nursing mothers not to breastfeed while taking BAVENCIO and for at least one month after the final dose [see Use in Specific Populations (8.2) ] .

Label text from the FDA structured product label by EMD Serono, Inc. (revised Aug 25, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Bavencio NDC products (1)

NDCStrength & formLabelerType
44087-3535Avelumab 20 mg/mL
Injection, Solution, Concentrate		EMD Serono, Inc.BLA

Frequently asked questions

What is Bavencio used for?

1 INDICATIONS AND USAGE BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for: Merkel Cell Carcinoma (MCC) Adults and pediatric patients 12 years and older with metastatic MCC. ( 1.1 , 14.1 ) Urothelial Carcinoma (UC) Maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy. ( 1.2 ,…

What are the side effects of Bavencio?

The following clinically significant 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) ] Major adverse cardiovascular events [see Warnings and Precautions (5.4) ] Most… See the full label for the complete list.

Who makes Bavencio?

Bavencio is listed by 1 labeler in the FDA NDC directory, including EMD Serono, Inc..