Safety and Efficacy Results of a Phase 1 Study of the Novel BCL2 Inhibitor Sonrotoclax (BGB-11417)
for Relapsed/Refractory Waldenström Macroglobulinemia

P1110

Chan Y. Cheah,1-3 Constantine S. Tam,4 Ramón García-Sanz,5 Mazyar Shadman,6,7 Sophie Leitch,8 Christopher D'Angelo,9 Lydia Scarfo,10 Yiqian Fang,11 Sheel Patel,12 Wei Ding,12 Haiyi Guo,13 Peter Browett14
Sir Charles Gairdner Hospital and Pathwest Laboratory Medicine, Nedlands, WA, Australia; 2Medical School, University of Western Australia, Crawley, WA, Australia; 3Linear Clinical Research, Nedlands, WA, Australia; 4Alfred Hospital and Monash University, Melbourne, VIC, Australia; 5Hospital Universitario de Salamanca, Salamanca, Spain;
6Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7University of Washington, Seattle, WA, USA; 8Te Whatu Ora, Health New Zealand, Waitemata, Auckland, New Zealand; 9University of Nebraska Medical Center, Omaha, NE, USA; 10Università Vita Salute and IRCCS Ospedale San Raffaele, Milan, Italy; 11BeiGene (Beijing) Co, Ltd, Beijing, China; 12BeiGene USA, Inc,San Mateo, CA, USA; 13BeiGene (Shanghai) Co, Ltd, Shanghai, China; 14Auckland City Hospital, Grafton, Auckland, New Zealand1• Across dose cohorts, the median age was 68.5 years and the median number

INTRODUCTIONof prior treatments was 2.5 (Table 1)• Waldenström macroglobulinemia (WM) is a rare, incurable, B-cell lymphoma,••

METHODS• BGB‑11417‑101 (NCT04277637) is a first‑in‑human, phase 1, open‑label, multicenter,••••

dose-escalation and -expansion study in patients with B-cell malignancies(Figure 1)
Eligible patients had R/R WM (disease that relapsed after or was refractory to≥1 prior systemic therapy) and required treatment per IWWM-7 criteria
The primary objectives of the study were to assess safety/tolerability, evaluate
the ramp-up dosing schedule, define the MTD, and determine the RP2D ofsonrotoclax monotherapy in patients with B-cell malignancies, including R/R WM
Responses were assessed per modified Owens 2013 criteria
Sonrotoclax was administered orally QD with a ramp-up schedule to mitigate
potential risk of TLS

Figure 1. BGB-11417-101 Study DesignSonrotoclax monotherapy dose findinga
R/R NHL, R/R CLL/SLL, R/R MCL, R/R WM
640 mg
320 mg– Twelve patients (60%) received prior BTK inhibitor therapy, nine (45%) of whom
had it as their last prior therapy

160 mg(n=8)

320 mg(n=5)

640 mg(n=1)

All(N=20)

Any TEAE

5 (83)

8 (100)5 (100)018 (90)

Grade ≥33 (50)

3 (38)

1 (20)

07 (35)

Serious TEAEs

3 (50)

2 (25)

1 (20)

06 (30)Deaths1 (17)

1 (13)

002 (10)a1 (17)

1 (13)

002 (10)b2 (33)

3 (38)005 (25)

00000

Table 1. Baseline Patient Characteristics
80 mg
(n=6)

160 mg(n=8)

320 mg(n=5)

640 mg(n=1)

All(N=20)

Study follow-up,
median (range),months23.4(7.6-27.1)

13.1(2.1-20.0)

4.1(2.7-8.5)

0.2(0.2-0.2)

12.3(0.2-27.1)

Age, median(range), years

65.5(48-79)69.5(61-87)65.0(61-77)84.0(84-84)

68.5(48-87)

Characteristic

Male sex, n (%)

6 (100)5 (63)

4 (80)

1 (100)

Led to sonrotoclax
discontinuation
Led to sonrotoclax
dose interruption
Led to sonrotoclax
dose reduction

16 (80)aECOG PS
03 (50)

20MYD88 mutation,n/tested (%)
CXCR4 mutation,n/tested (%)

4/4 (100)
1/4 (25)

2 (25)
5 (63)
1 (13)
4/4 (100)
1/4 (25)

1 (20)
4 (80)
0
2/2 (100)
1/2 (50)01 (100)

13 (65)0
1/1 (100)

Pyrexia

11/11 (100)0/1 (0)No. of lines of priorsystemic therapy,
median (range)

80 mg
The safety monitoring committee reviewed dose-level cohort data before dose escalation.

3 (1-8)2.5 (1-9)

1 (1-8)3 (3-3)• As of February 4, 2024, a total of 20 patients with R/R WM had received

1sonrotoclax (80, 160, 320, or 640 mg), and 14 remained on treatment (Figure 2)– Six patients (30%) discontinued treatment due to progressive disease (PD; n=4)

2

and AEs of multifocal neurological syndrome (n=1) and COVID-19 (n=1);
neither AE was considered related to sonrotoclax by the investigator≥3

Figure 2. Patient Disposition

Prior BTK
inhibitor, n (%)

All patients dosed to date in BGB-11417-101
N=348

Sonrotoclax monotherapy
n=123 (all NHL cohorts)

R/R WM n=20
Median follow-up: 12.3 months(range, 0.2-27.1 months)
80 mg: n=6160 mg: n=8320 mg: n=5640 mg: n=1

Sonrotoclax + zanubrutinib
n=200(TN and R/R CLL and R/R MCL cohorts)
R/R CLL/SLL sonrotoclax + zanubrutinib
EHA 2024 Abstract S156
R/R MCL sonrotoclax + zanubrutinib
EHA 2024 Abstract P1112

BTK inhibitor as
last therapy, n (%)
Prior BTK inhibitor
duration, median(range), months

Sonrotoclax + obinutuzumab± zanubrutinibn=25(CLL cohorts)

1 (17)
4 (67)
4 (67)−

3 (38)
1 (13)
4 (50)
4 (50)−0
1 (20)
3 (60)−

8 (40)

02 (10)1 (100)10 (50)1 (100)13.1(1.1-25.1)

68.5(68.5-68.5)

Off treatmentn=6
PD: n=4AE: n=2Contusion

15160 mg

105

Grade 1/2

5Grade ≥310X160 mg

Neutropenia combines preferred terms neutrophil count decreased and neutropenia. b Thrombocytopenia combines preferredterms platelet count decreased and thrombocytopenia.

X160 mg• Response rates are shown in Figure 4; the 1 patient in the 640-mg cohort was not

X320 mg

510152025303540ayet response evaluable

100XORRb
88%

ORRb
80%
20ORRb79%53.7(1.1-85.4)• An overall summary of TEAEs in patients with R/R WM is shown in Table 2– Four patients died while on study due to PD (n=2), COVID-19 pneumonia (n=1),

60

1147

• The most common any-grade TEAEs across cohorts were anemia (35%),

20

COVID-19 (30%), and pyrexia (25%) (Figure 3)

38VGPRPRMR17SD
21173820170• No laboratory or clinical TLS was seen regardless of target dose
• One patient in the 160-mg dose group experienced a DLT of grade 3

Study follow-upd,median (range),months

11580 mg(n=6)

160 mg(n=8)c320 mg(n=5)

All patients(N=19)

23.4(7.6-27.1)

13.1(2.1-20.0)

4.1(2.7-8.5)

12.3(0.2-27.1)

Responses were assessed per modified Owens 2013 criteria. b ORR was defined as response of MR or better. c One patient dieddue to a COVID-19 infection before a post-baseline response assessment. d For all patients as treated (N=20).
MR, minor response; NA, not assessable; VGPR, very good partial response.
aVGPR
PRMRSD320 mg

PDNE

X320 mg

X

640 mgOngoing treatment
Death
Reached target dose
24

68

1012

1416

1820

2224

26

28

30

3234

Time since first dose, months

PDand multi-organ failure (n=1); neither TEAE was related to sonrotoclax

640 mg06040320 mg

320 mg1380160 mg

320 mgFigure 4. Response Ratesa
ORRb67%80 mg

160 mg
160 mgLDi, longest diameter; PS, performance status.

•160 mg

X9 (45)febrile neutropenia which resolved after 2 days without dose reduction duringramp-up day 2 on 10 mg of sonrotoclax
Dose escalation is ongoing at 640 mg, with no MTD reached at the time ofdata cut-off

X160 mg50

60.7
48.4(55.3-85.4) (19.4-54.5)

80 mg

15Fatigue

12 (60)−X

Headache

5Patients, %080 mg

160 mg04 (80)X

15

Thrombocytopeniab

1 (17)

580 mgRash

2.5 (1-9)– The most common grade ≥3 TEAE was anemia (20%)

On treatment
n=1480 mg: n=2160 mg: n=6320 mg: n=5640 mg: n=115X

15No. of lines of prior systemic therapy, n (%)

RESULTS80 mg

20Dose80 mg

Nausea3/11 (27)

Prior therapy

Figure 5. Treatment Duration and Investigator-Assessed Responses

2025

Neutropeniaa• Preliminary antitumor activity was encouraging in thisheavily pretreated population, with high and durable
responses across all tested dose levels• Further evaluation of sonrotoclax monotherapy in patientswith R/R WM is ongoing in a pivotal study (BGB-11417-203)

80 mg

30Pruritus– No laboratory or clinical TLS events were observed

Sonrotoclax monotherapy(N=20)
15

COVID-19

1 (5)• Sonrotoclax monotherapy was well tolerated in patients withR/R WM; the MTD was not reached

X6 (30)AnemiaCONCLUSIONS

PriorBTKi

COVID-19 pneumonia, pneumonia. b COVID-19, multifocal neurological syndrome (no further information).

Figure 3. TEAEs in ≥3 Patients
3 (50)

1160 mgaPatients, n (%)

80 mg
(n=6)

Patients, %•and more tolerable and effective treatments are needed for patients who
experience progression on standard treatments1Inhibition of BCL2 has demonstrated antitumor activity in patients with WM;
however, no BCL2 inhibitors are currently approved2Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selectiveand pharmacologically potent inhibitor of BCL2 than venetoclax with a shorter
half-life and no accumulation3
Here, updated safety and efficacy data are presented for patients withrelapsed/refractory (R/R) WM treated with sonrotoclax monotherapy in theongoing BGB-11417-101 study

Table 2. TEAE Summary

BTKi, BTK inhibitor; MR, minor response; NE, not evaluable; VGPR, very good partial response.

REFERENCES

1. Castillo JJ, et al. Lancet Haem. 2020;7(11):e827-837.
2. Castillo JJ, et al. J Clin Oncol. 2022;40(1):63-71.
3. Hu N, et al. AACR 2020. Abstract 3077.

DISCLOSURESCYC: Consultancy, honoraria, membership on an entity's board of directors or advisory committees: Roche, Janssen, MSD, Gilead, Ascentage Pharma,AstraZeneca, Lilly. CST: Research funding: Janssen, AbbVie, BeiGene; Honoraria: Janssen, AbbVie, BeiGene, Loxo, AstraZeneca. RGS: Consultancy:Janssen, BeiGene; Research funding: Gilead, Takeda; Honoraria: Janssen, Takeda, BeiGene, Incyte, Astellas, Novartis, GSK; Patents and royalties: IVS(institutional agreement); Speakers bureau: Janssen, BeiGene. MS: Consulting, advisory boards, steering committees or data safety monitoring committees:
AbbVie, Genentech, AstraZeneca, Genmab, Janssen, BeiGene, BMS, MorphoSys/Incyte, Kite Pharma, Eli Lilly, Mustang Bio, Fate Therapeutics, Nurix, Merck;
Institutional research funding: Mustang Bio, Genentech, AbbVie, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, Vincerx; Stock options:
Koi Biotherapeutics; Employment: BMS (spouse). SL: Nothing to disclose. CD: Research funding: BMS, Fate Therapeutics, BeiGene; Consultancy,participation in advisory boards: AbbVie, ONO Pharmaceutical Co, BMS, Seagen. LS: Advisory board: AbbVie, AstraZeneca, Janssen. YF, SP, HG:Employment and stock with BeiGene. WD: Research funding: BeiGene; Grants: Merck, AstraZeneca, DTRM Pharma, Octapharma, BeiGene; Advisory board:
Kite Pharma; Employment: BeiGene. PB: Honoraria: AbbVie; Member of the board of directors or advisory committee: MSD, Janssen.

ACKNOWLEDGMENTS

The authors thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers. This study wassponsored by BeiGene, Ltd. Medical writing was provided by Angela R. Eder, PhD, and Brittany Gifford, PharmD, of Nucleus Global, an Inizio company, andsupported by BeiGene.

Presented at the EHA2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain