b'FOR ADULT PATIENTS WITH MANTLE CELL LYMPHOMA (MCL) 3BRUKINSATHE BTK INHIBITOR DEMONSTRATEDTO PROVIDE COMPLETE AND SUSTAINED INHIBITION 1,2POWERFUL RESPONSES 1 DEMONSTRATED SAFETY P ROFILE 1STUDY 206 | PET-BASED1 STUDY 003 | CT-BASED1 The most common adverse reactions ( 20%) included neutrophil count decreased, plateletcount decreased, upper respiratory tract infection, 84 % 84 % white blood cell count decreased, hemoglobin ORR ORR decreased, rash, bruising, diarrhea, and cough. (95% CI: 74, 91) (95% CI: 67, 95)The efficacy of BRUKINSA was IRC-assessed in 2 clinical trials that 59 % 22 % included a total of 118 adult patients with MCL who received at least 1 prior therapy. Tumor response was according to the 2014 Lugano classification for both studies, and the primary efficacy endpoint was CR CR ORR as assessed by an IRC. Study BGB-3111-206 (Study 206): N=86, Phase 2, open-label, multicenter, single-arm trial; PET scans were required 19.5 mo 18.5 mo for response assessment. Study BGB-3111-AU-003 (Study 003): N=32, Phase 1/2, open-label, global, multicenter, single-arm trial; PET scans were not required for response assessment and the majority of patients MEDIAN DOR MEDIAN DOR were assessed by CT scan.(95% CI: 16.6, NE) (95% CI: 12.6, NE) BTK=Brutons tyrosine kinase; CI=confidence interval; CR=complete response; CT=computed tomography; DOR=duration of response; IRC=independent review committee; NE=not estimable; ORR=overall Median follow-up time was 18.4 months for response rate; PET=positron emission tomography.Study 206 and 18.8 months for Study 003 3BRUKINSA (zanubrutinib) is a kinase inhibitor indicated for the treatment of adult patients with mantle cell 100%, 24-hour inhibition of BTK was maintained in peripheral lymphoma (MCL) who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon blood when taken as 160 mg twice a day or 320 mg once a day. verification and description of clinical benefit in a confirmatory trial.*1,2IMPORTANT SAFETY INFORMATIONWARNINGS AND PRECAUTIONS InfectionsMonitor complete blood counts during treatment and treatAdministration of zanubrutinib to pregnant rats during theOf the 118 patients with MCL treated with BRUKINSA, 8 (7%)INDICATIONHemorrhageFatal and serious infections (including bacterial, viral, using growth factor or transfusions, as needed. period of organogenesis caused embryo-fetal toxicitypatients discontinued treatment due to adverse reactionsBRUKINSA is a kinase inhibitor indicated for the treatment Fatal and serious hemorrhagic events have occurred inor fungal) and opportunistic infections have occurred inSecond Primary Malignanciesincluding malformations at exposures that were 5 timesin the trials. The most frequent adverse reaction leading toof adult patients with mantle cell lymphoma (MCL) who patients with hematological malignancies treated withpatients with hematological malignancies treated withSecond primary malignancies, including non-skinhigher than those reported in patients at the recommendedtreatment discontinuation was pneumonia (3.4%). Onehave received at least one prior therapy.BRUKINSA monotherapy. Grade 3 or higher bleedingBRUKINSA monotherapy. Grade 3 or higher infectionscarcinoma, have occurred in 9% of patients treated withdose of 160 mg twice daily. Advise women to avoid becoming(0.8%) patient experienced an adverse reaction leading toThis indication is approved under accelerated approval events including intracranial and gastrointestinaloccurred in 23% of patients treated with BRUKINSABRUKINSA monotherapy. The most frequent secondpregnant while taking BRUKINSA and for at least 1 week afterdose reduction (hepatitis B). based on overall response rate. Continued approval for this hemorrhage, hematuria and hemothorax have beenmonotherapy. The most common Grade 3 or higher infectionprimary malignancy was skin cancer (basal cell carcinomathe last dose. Advise men to avoid fathering a child duringDRUG INTERACTIONS indication may be contingent upon verification and reported in 2% of patients treated with BRUKINSAwas pneumonia. Infections due to hepatitis B virus (HBV)and squamous cell carcinoma of skin), reported in 6% oftreatment and for at least 1 week after the last dose. monotherapy. Bleeding events of any grade, includingreactivation have occurred.patients. Advise patients to use sun protection. If this drug is used during pregnancy, or if the patientCYP3A Inhibitors: When BRUKINSA is co-administered with adescription of clinical benefit in a confirmatory trial.purpura and petechiae, occurred in 50% of patientsConsider prophylaxis for herpes simplex virus,becomes pregnant while taking this drug, the patient strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg onceReferences: 1. BRUKINSA [package insert]. BeiGene, Ltd; 2019. 2. Tam C, treated with BRUKINSA monotherapy.pneumocystis jiroveci pneumonia and other infectionsCardiac Arrhythmias should be apprised of the potential hazard to a fetus. daily.For coadministration with a moderate CYP3A inhibitor,Trotman J, Opat S, et al. Phase 1 study of the selective BTK inhibitor according to standard of care in patients who are atAtrial fibrillation and atrial flutter have occurred inreduce BRUKINSA dose to 80 mg twice daily. zanubrutinib in B-cell malignancies and safety and efficacy evaluation in Bleeding events have occurred in patients with andincreased risk for infections. Monitor and evaluate patients2% of patients treated with BRUKINSA monotherapy.ADVERSE REACTIONS CYP3A Inducers: Avoid coadministration with moderate orCLL. Blood. 2019;134(11):851-859. 3. Data on file. BeiGene, Ltd. 2019.without concomitant antiplatelet or anticoagulationfor fever or other signs and symptoms of infection andPatients with cardiac risk factors, hypertension, andThe most common adverse reactions in 10% of patients strong CYP3A inducers. Please see Brief Summary of full Prescribing Information therapy. Co-administration of BRUKINSA with antiplatelet treat appropriately.acute infections may be at increased risk. Grade 3 orwho received BRUKINSA were decreased neutrophil counton the following pages.or anticoagulant medications may further increase thehigher events were reported in 0.6% of patients treated(53%), decreased platelet count (39%), upper respiratory SPECIFIC POPULATIONSrisk of hemorrhage. Cytopeniaswith BRUKINSA monotherapy. Monitor signs and tract infection (38%), decreased white blood cell countHepatic Impairment:The recommended dose ofMonitor for signs and symptoms of bleeding. DiscontinueGrade 3 or 4 cytopenias, including neutropenia (27%),symptoms for atrial fibrillation and atrial flutter(30%), decreased hemoglobin (29%), rash (25%), BRUKINSA for patients with severe hepatic impairment is BRUKINSA if intracranial hemorrhage of any grade occurs.thrombocytopenia (10%) and anemia (8%) based onand manage as appropriate. bruising (23%), diarrhea (20%), cough (20%),80 mg orally twice daily.Consider the benefit-risk of withholding BRUKINSA for 3-7laboratory measurements, were reported in patientsEmbryo-Fetal Toxicitymusculoskeletal pain (19%), pneumonia (18%), urinarydays pre- and post-surgery depending upon the type oftreated with BRUKINSA monotherapy. Based on findings in animals, BRUKINSA can cause fetaltract infection (13%), hematuria (12%), fatigue (11%), surgery and the risk of bleeding. harm when administered to a pregnant woman.constipation (11%), and hemorrhage (10%).*The clinical significance of 100% occupancy has not been established.BRUKINSA and BeiGene are trademarks owned by BeiGene, Ltd.BeiGene, Ltd. 2020 All Rights Reserved. 0320-BRU-PRC-012 03/2020 LEARN MORE AT BRUKINSA.com15434_3_Brukinsa_BrandedHCP_PostApproval_Compendium_0620_RL.indd 1-2 5/1/20 11:53 AM'