Necitumumab

1 INDICATIONS AND USAGE PORTRAZZA™ is an epidermal growth factor receptor (EGFR) antagonist indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. ( 1.1 ) Limitation of Use: PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung cancer. ( 1.2 , 5.6 , 14.2 ) 1.1 Squamous Non-Small Cell Lung Cancer (NSCLC) PORTRAZZA™ is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. 1.2 Limitation of Use PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung cancer [see Warnings and Precautions ( 5.6 ) and Clinical Studies ( 14.2 )] .

6 ADVERSE REACTIONS The following adverse drug reactions are discussed in greater detail in other sections of the label: Cardiopulmonary Arrest [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Hypomagnesemia [see Boxed Warning and Warnings and Precautions ( 5.2 )] . Venous and Arterial Thromboembolic Events [see Warnings and Precautions ( 5.3 )] . Dermatologic Toxicities [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.4 )] . Infusion-Related Reactions [see Dosage and Administration ( 2.2 , 2.3 ) and Warnings and Precautions ( 5.5 )] . Non-Squamous NSCLC - Increased Toxicity and Increased Mortality [see Warnings and Precautions ( 5.6 ) and Clinical Studies ( 14.2 )] .

8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action, PORTRAZZA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development. The absence of EGFR signaling has resulted in embryolethality as well as post-natal death in animals (see Data) . No animal reproduction studies have been conducted with necitumumab.

WARNING: CARDIOPULMONARY ARREST and HYPOMAGNESEMIA Cardiopulmonary arrest and/or sudden death occurred in 3.0% of patients treated with PORTRAZZA in combination with gemcitabine and cisplatin. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after PORTRAZZA administration [see Warnings and Precautions ( 5.1 , 5.2 )] . 5 WARNINGS AND PRECAUTIONS Cardiopulmonary Arrest : Closely monitor serum electrolytes during and after PORTRAZZA. ( 5.1 ) Hypomagnesemia : Monitor prior to each infusion and for at least 8 weeks following the completion of PORTRAZZA. Withhold PORTRAZZA for Grade 3 or 4 electrolyte abnormalities; subsequent cycles of PORTRAZZA may be administered in these patients once electrolyte abnormalities have improved to Grade ≤2. Replete electrolytes as necessary. ( 5.2 ) Venous and Arterial Thromboembolic Events (VTE and ATE) : Discontinue PORTRAZZA for severe VTE or ATE. ( 5.3 ) Dermatologic Toxicities : Monitor for dermatologic toxicities and withhold or discontinue PORTRAZZA for severe toxicity. Limit sun exposure. 4 CONTRAINDICATIONS None None ( 4 )