b'65Double the median PFS achieved with LENVIMA vs sorafenib 1,3See aspectrum Statistically superior PFS (mRECIST) per independent radiology reviewof results 1.0 7.3LENVIMA0.9 0.8 MONTHS(95% CI:0.7 5.6-7.5)Probability 0.6sorafenib 36% 0.5Let LENVIMAchangethe way you view treatment0.4 HR: 0.64 REDUCED (95% CI: 0.55-0.75); 0.3 P0.001 RISK OFin unresectable HCC 0.2 3.6 PROGRESSIONrst-line MONTHS OR DEATH(95% CI:0.1 3.6-3.7) 0.00 3 6 9 12 15 18 21 24 27 30 33 36 39REFLECT: in a large (N=954), phase 3, multicenter,Statistical superiority vs sorafenib in selectTime (months) Patients on LENVIMA randomized, open-label trial in patients withsecondary ecacy endpoints, PFS and ORR,Number of subjects at risk remained progression previously untreated unresectable HCC vsaccording to mRECIST 1 LENVIMA 478 324 182 128 64 34 24 17 8 5 2 1 0 0 free for twice as long as 1,2 sorafenib 476 222 85 59 33 24 19 16 9 4 2 0 0 0 those on sorafenib 1sorafenib, LENVIMA met the primary endpoint Nearly 3.5X ORR, 41% with LENVIMA 13.6-month median OS, proven noninferior tovs 12% with sorafenib 1Number of events: 311 (65%) with LENVIMA and 323 (68%) with sorafenib.1sorafenib (12.3 months) 1Complete response: 2.1% (n=10) with LENVIMA An independent assessment using RECIST 1.1 criteria demonstrated a median PFS of 7.3 months with LENVIMA vs HR: 0.92 (95% CI: 0.79-1.06)* vs 0.8% (n=4) with sorafenib 3.6 months with sorafenib (HR: 0.65 [95% CI 0.56-0.77]) 1Number of events: 351 (73%) with LENVIMAPartial response: 38.5% (n=184) with LENVIMANumber of events: 307 (64%) with LENVIMA vs 320 (67%) with sorafenib.1and 350 (74%) with sorafenib vs 11.6% (n=55) with sorafenibLENVIMA did not demonstrate a statistically95% CI: 36%-45% vs 95% CI: 10%-16%; P0.001 Adverse reaction pro le 1signi cant improvement in OS vs sorafenib 1 An independent assessment using RECIST 1.1 criteriaThe most common adverse reactions observed in LENVIMA-treated patients (20%) were, in order of decreasing demonstrated 19% ORR with LENVIMA (95% CI:frequency, hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, * Based on stratifi ed Cox-model. The noninferiority margin for the HR of15%-22%) vs 7% with sorafenib (95% CI: 4%-9%) 1 palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.LENVIMA vs sorafenib is 1.08.1 Complete response: 0.4% (n=2) with LENVIMA vs 0.2% (n=1) HCC=hepatocellular carcinoma; REFLECT=A Multicenter, Randomized, Open-label, Phase 3 Trial to Compare the EFfi cacy and Safety of LEnvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With UnreseCtable HepaTocellular Carcinoma; OS=overall survival; HR=hazard ratio; CI=confi dence interval; PFS=progression-free survival; ORR=objective response Partial response: 18.4% (n=88) with LENVIMA vsrate; mRECIST=modifi ed Response Evaluation Criteria; RECIST=Response Evaluation Criteria in Solid Tumors. 6.3% (n=30) In REFLECT, patients enrolled had Child-Pugh A and BCLC Stage C or B HCC and were ineligible for local liver-directed therapy; had an ECOG PS of 0 or 1; had received no prior systemic therapy for HCC; and had 1 measurable target lesion according to mRECIST for HCC. Patients were randomized (1:1) to receive LENVIMA (12 mg for baseline body weight 60 kg or 8 Based on a masked independent imaging review according to mRECIST.2mg for baseline body weight 60 kg) orally once daily or sorafenib 400 mg orally twice daily until radiological disease progression or unacceptable toxicity. The primary endpoint was OS. REFLECT was designed to show the noninferiority of LENVIMA to sorafenib for OS. Select secondary effi cacy endpoints were PFS and ORR according to mRECIST for HCC.INDICATIONAmong patients receiving LENVIMA with pembrolizumab, arterial thromboticIMPORTANT SAFETY INFORMATION ms occurred in 6%. In HCC, QTc interval increases of 60 ms occurred in 8% LENVIMA is indicated for the fi rst-line treatment of patients withevents of any severity occurred in 5% of patients in CLEAR, includingWarnings and Precautions (contd) of LENVIMA-treated patients and QTc interval 500 ms occurred in 2%.unresectable hepatocellular carcinoma (HCC). myocardial infarction (3.4%) and cerebrovascular accident (2.3%). Monitor and correct electrolyte abnormalities at baseline and periodically Permanently discontinue following an arterial thrombotic event. The safetyProteinuria. In DTC and HCC, proteinuria was reported in 34% and 26%during treatment. Monitor electrocardiograms in patients with congenital IMPORTANT SAFETY INFORMATION of resuming after an arterial thromboembolic event has not beenof LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred inlong QT syndrome, congestive heart failure, bradyarrhythmias, or those who Warnings and Precautions established, and LENVIMA has not been studied in patients who have had11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred inare taking drugs known to prolong the QT interval, including Class Ia and III an arterial thromboembolic event within the previous 6 months. 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitorantiarrhythmics. Withhold and resume at reduced dose upon recovery Hypertension. In DTC (differentiated thyroid cancer), hypertension occurred infor proteinuria prior to initiation and periodically during treatment. Ifbased on severity.73% of patients on LENVIMA (44% grade 3-4). In RCC (renal cell carcinoma),Hepatotoxicity. Across clinical studies enrolling 1327 LENVIMA-treatedurine dipstick proteinuria 2+ is detected, obtain a 24-hour urine protein.hypertension occurred in 42% of patients on LENVIMA + everolimus (13% gradepatients with malignancies other than HCC, serious hepatic adverseWithhold and resume at reduced dose upon recovery or permanentlyHypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of 3). Systolic blood pressure 160 mmHg occurred in 29% of patients, and 21%reactions occurred in 1.4% of patients. Fatal events, including hepaticdiscontinue based on severity. LENVIMA-treated patients. In 65% of cases, hypocalcemia improved had diastolic blood pressure 100 mmHg. In HCC (hepatocellular carcinoma),failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% ofDiarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrheaor resolved following calcium supplementation with or without dose hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3).patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA- occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% ofinterruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred Grade 4 hypertension was not reported in HCC. treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3%LENVIMA + everolimustreated patients (19% grade 3). Diarrhea was thein 6% of LENVIMA + everolimustreated patients. In HCC, grade 3 Serious complications of poorly controlled hypertension have been reported.of LENVIMA-treated patients; 2% of patients discontinued LENVIMA duemost frequent cause of dose interruption/reduction, and diarrhea recurredhypocalcemia occurred in 0.8% of LENVIMA-treated patients. Control blood pressure prior to initiation. Monitor blood pressure after 1to hepatic encephalopathy, and 1% discontinued due to hepatic failure. despite dose reduction. Promptly initiate management of diarrhea. Withhold week, then every 2 weeks for the fi rst 2 months, and then at least monthlyMonitor liver function prior to initiation, then every 2 weeks for the fi rstand resume at reduced dose upon recovery or permanently discontinue Visitthereafter during treatment. Withhold and resume at reduced dose when2 months, and at least monthly thereafter during treatment. Monitorbased on severity. hypertension is controlled or permanently discontinue based on severity. patients with HCC closely for signs of hepatic failure, including hepaticFistula Formation and Gastrointestinal Perforation. Of the 799 www.LENVIMA.com/hcpCardiac Dysfunction. Serious and fatal cardiac dysfunction can occur withencephalopathy. Withhold and resume at reduced dose upon recovery orpatients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC,permanently discontinue based on severity. HCC, fi stula or gastrointestinal perforation occurred in 2%. Permanentlyto learn moregrade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treatedRenal Failure or Impairment. Serious including fatal renal failure ordiscontinue in patients who develop gastrointestinal perforation of any patients. Monitor for clinical symptoms or signs of cardiac dysfunction.impairment can occur with LENVIMA. Renal impairment was reported inseverity or grade 3-4 fi stula.Withhold and resume at reduced dose upon recovery or permanently14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively.QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred discontinue based on severity. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTCin 9% of LENVIMA-treated patients and QT interval prolongation of 500 and 2% of patients with HCC, including 1 fatal event in each study. Inms occurred in 2%. In RCC, QTc interval increases of 60 ms occurred in Arterial Thromboembolic Events. Among patients receiving LENVIMARCC, renal impairment or renal failure was reported in 18% of LENVIMA +11% of patients receiving LENVIMA + everolimus and QTc interval 500 or LENVIMA + everolimus, arterial thromboembolic events of any severityeverolimustreated patients (10% grade 3).occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanentlyPlease see additional Important Safety Information throughout discontinue for renal failure or impairment based on severity. and accompanying Brief Summary of Prescribing Information.84724_A-SIZE_PB.indd 1-2 9/24/21 1:15 PM'