Zanubrutinib in marginal zone lymphoma (MZL)

January 2023

The Phase 2 MAGNOLIA Trial Zanubrutinib is approved in the EU as a monotherapy for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy. Prescribing information (PI) may vary depending on local approval in each country. Therefore, before prescribing any product, always refer to local authorities concerning reimbursement status and to local materials such as the PI and/or the summary of product characteristics (SmPC) for guidance on prescribing.

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MAGNOLIA study design Study identifier:

BGB-3111-214, MAGNOLIA, NCT03846427

R/R MZL (N=68)

Zanubrutinib monotherapy (160 mg BID)

Primary endpoint:

ORR by IRC using Lugano 2014 classification1

Secondary endpoints:

ORR by PI, PFS, OS, DoR, safety

Key eligibility criteria • Age ≥18 years • Histologically confirmed MZL including splenic, nodal, and extranodal subtypes • Previously received ≥1 CD20-directed regimen, with documented failure to achieve at least partial response or documented progressive disease after the most recent systemic treatment • Measurable disease by computerized tomography or magnetic resonance imaging • Adequate organ function • No prior BTK inhibitor exposure

BID, twice a day; BTK, Bruton’s tyrosine kinase; CD20, cluster of differentiation 20; DoR, duration of response; IRC, independent review committee; MZL, marginal zone lymphoma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PI, principal investigator; R/R, relapsed/refractory. 1. Cheson BD, et al. J Clin Oncol. 2014;32(27):3059-3067. 2. Clinicaltrials.gov published online 2021. https://clinicaltrials.gov/ct2/show/ NCT03846427. 3. Opat et al, Abstract #234 presented at ASH 2022. This study is registered at ClinicalTrials.gov (NCT03846427). Zanubrutinib is approved in the EU as a monotherapy for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy. Prescribing information (PI) may vary depending on local approval in each country. Therefore, before prescribing any product, always refer to local authorities concerning reimbursement status and to local materials such as the PI and/or the summary of product characteristics (SmPC) for guidance on prescribing.

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Patient disposition Enrolled/safety population (N=68) Median study follow-up: 28 months (range, 1.6-32.9)

Efficacy population (n=66)

Not evaluable for efficacy (n=2)a

Continuing zanubrutinib on LTE1b (n=31) On zanubrutinib at end of study but did not rollover to LTE1 (n=3) Off treatment (n=34) • PD (n=24) • AEc (n=5) • Investigator decisiond (n=4) • Withdrawal by patient (n=1)

Data cutoff: 4 May 2022. aTwo patients were excluded owing to lack of central confirmation of MZL. bBGB-3111-LTE1 is a BeiGene-sponsored, global, open-label extension study (NCT04170283). c Five patients discontinued treatment owing to AEs (2 patients with fatal COVID-19 pneumonia; 1 patient with pyrexia later attributed to disease progression; 1 patient with fatal myocardial infarction in a patient with preexisting cardiovascular disease; 1 patient who died from septic encephalopathy after bladder surgery (in CR at the time of death).dFour patients discontinued per investigator decision (3 patients required prohibited medications; 1 patient due to lack of clinical benefit). AE, adverse event; CR, complete remission; LTE, long-term extension; PD, progressive disease. 1. Opat et al, Abstract #234 presented at ASH 2022. This study is registered at ClinicalTrials.gov (NCT03846427). Zanubrutinib is approved in the EU as a monotherapy for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy. Prescribing information (PI) may vary depending on local approval in each country. Therefore, before prescribing any product, always refer to local authorities concerning reimbursement status and to local materials such as the PI and/or the summary of product characteristics (SmPC) for guidance on prescribing.

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Baseline demographics and disease history Characteristics, n (%) Median age (range), years ≥65 ≥75 Male ECOG PS 0/1a

Total (N=68) 70 (37-95) 41 (60) 19 (28) 36 (53) 63 (93)

MZL subtypes Extranodal Nodal Splenic Unknown

26 (38) 26 (38) 12 (18) 4 (6)

Disease status Relapsed Refractory Stage III/IV FDG-avid (by IRC) Extranodal site involvement Bone marrow infiltration Median prior lines of systemic therapy (range) Immunochemotherapy Rituximab monotherapy

44 (65) 22 (32) 59 (87) 61 (90) 53 (78) 29 (43) 2 (1-6) 61 (90)b 7 (10)

Overall, 43% of patients had ECOG 1/2. bRituximab-based chemotherapy in most patients (n=60; 88%). ECOG PS, Eastern Cooperative Oncology Group performance score; FDG, fluorodeoxyglucose; IRC, independent review committee; MZL marginal zone lymphoma. 1. Opat et al, Abstract #234 presented at ASH 2022. This study is registered at ClinicalTrials.gov (NCT03846427). a

Zanubrutinib is approved in the EU as a monotherapy for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy. Prescribing information (PI) may vary depending on local approval in each country. Therefore, before prescribing any product, always refer to local authorities concerning reimbursement status and to local materials such as the PI and/or the summary of product characteristics (SmPC) for guidance on prescribing.

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Best overall response by IRC and investigator assessment (N=66)a IRC

INV

PET and/or CT (primary endpoint)b

CT only (sensitivity analysis)f

PET and/or CT

45 (68) [55.6, 79.1] 30%. dFive (7.6%) patients with stable disease are remaining on study treatment (after 12-18 cycles). e Includes one patient with FDG-avid disease who missed the PET scan at cycle 3 and was assessed as non-PD; CT showed stable disease at cycle 3. fAdditional sensitivity analysis using CT-based Lugano criteria for all 66-evaluable patients regardless of PET status at baseline. CI, confidence interval; CR, complete response; CT, computerized tomography; FDG, fluorodeoxyglucose; INV, investigator; IRC, independent review committee; MZL, marginal zone lymphoma; ORR, overall response rate; PD, progressive disease; PET, positron emission tomography; PR, partial response; SD, stable disease. 1. Opat et al, Abstract #234 presented at ASH 2022. This study is registered at ClinicalTrials.gov (NCT03846427). Zanubrutinib is approved in the EU as a monotherapy for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy. Prescribing information (PI) may vary depending on local approval in each country. Therefore, before prescribing any product, always refer to local authorities concerning reimbursement status and to local materials such as the PI and/or the summary of product characteristics (SmPC) for guidance on prescribing.

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Subgroup analysis of ORR by IRC Subgroup

Patients/response

ORR, % (95% CI)a

All patients

45/66

68.2 (55.6, 79.1)

Age group